{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:31:45Z","timestamp":1792690305259,"version":"4.5.0"},"reference-count":140,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Solid organ transplantation, a major breakthrough in modern medicine, has saved countless patients with end-stage organ failure. However, immune rejection remains the primary obstacle to transplant success. As the central effector cells of adaptive immunity, T cells drive acute rejection by directly recognizing donor alloantigens (such as MHC molecules) or indirectly recognizing processed donor antigens presented by antigen-presenting cells. Recent studies have revealed the dual roles of distinct T cell subsets in rejection or tolerance: pro-inflammatory Th1, Th2, Th17, and CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells(CTLs) exacerbate tissue damage by secreting cytokines such as IFN-\u03b3 and IL-17, whereas regulatory T cells(Tregs) promote graft tolerance by suppressing effector T cell activation and maintaining immune homeostasis. This article systematically reviews the molecular mechanisms of T cell-mediated rejection, functional heterogeneity among T cell subsets, and their differential impacts on various types of solid organ transplants.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1787579","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:19:00Z","timestamp":1774502340000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The dual role of T cells in solid organ transplant rejection and immune tolerance"],"prefix":"10.3389","volume":"17","author":[{"given":"Zixuan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Weifang People\u2019s Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Miao","sequence":"additional","affiliation":[{"name":"Weifang People\u2019s Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubao","family":"Sun","sequence":"additional","affiliation":[{"name":"Weifang People\u2019s Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Weifang People\u2019s Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Ding","sequence":"additional","affiliation":[{"name":"Weifang People\u2019s Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Weifang People\u2019s Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niannian","family":"Li","sequence":"additional","affiliation":[{"name":"Weifang People\u2019s Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1097\/SLA.0000000000004071","article-title":"Transplant oncology in primary and metastatic liver tumors: principles, evidence, and opportunities","volume":"273","author":"Sapisochin","year":"2021","journal-title":"Ann Surg"},{"key":"B2","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s41392-023-01377-9","article-title":"Activation of immune signals during organ transplantation","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduction Targeted Ther"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.688460","article-title":"Harnessing mechanisms of immune tolerance to improve outcomes in solid organ transplantation: a review","volume":"12","author":"Slepicka","year":"2021","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.746889","article-title":"Utilization of treg cells in solid organ transplantation","volume":"13","author":"Juneja","year":"2022","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s41581-022-00600-0","article-title":"Activation and regulation of alloreactive T cell immunity in solid organ transplantation","volume":"18","author":"Duneton","year":"2022","journal-title":"Nat Rev Nephrol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1340","article-title":"Roles for innate immunity in combination immunotherapies","volume":"77","author":"Moynihan","year":"2017","journal-title":"Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.714","article-title":"The interaction of innate immune and adaptive immune system","volume":"5","author":"Wang","year":"2024","journal-title":"Medcomm"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nri911","article-title":"Functional significance of the perforin\/granzyme cell death pathway","volume":"2","author":"Trapani","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.9","article-title":"Memory T cells in organ transplantation: progress and challenges","volume":"12","author":"Espinosa","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.004","article-title":"Principles of regulatory T cell function","volume":"56","author":"Dikiy","year":"2023","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114624","article-title":"Exploiting regulatory T cells (tregs): cutting-edge therapy for autoimmune diseases","volume":"155","author":"Hassan","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3123","article-title":"Control of adaptive immunity by the innate immune system","volume":"16","author":"Iwasaki","year":"2015","journal-title":"Nat Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00680","article-title":"The pivotal role of regulatory T cells in the regulation of innate immune cells","volume":"10","author":"Okeke","year":"2019","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00378.x","article-title":"The T cell as a bridge between innate and adaptive immune systems: implications for the kidney","volume":"61","author":"Rabb","year":"2002","journal-title":"Kidney Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1031924","article-title":"The adaptive immune system in early life: The shift makes it count","volume":"13","author":"Pieren","year":"2022","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-0716-3754-8_3","article-title":"T cell subsets and immune homeostasis","volume-title":"Immune Homeostasis","author":"Wu","year":"2024"},{"key":"B17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-3-030-10811-3_3","article-title":"T cell subsets and T cell-mediated immunity","volume-title":"Nijkamp and Parnham\u2019s Principles of Immunopharmacology","author":"Broere","year":"2019"},{"key":"B18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1146\/annurev-immunol-061020-053702","article-title":"Cytokine regulation and function in T cells","volume":"39","author":"Dong","year":"2021","journal-title":"Annu Rev Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1146\/annurev.immunol.19.1.23","article-title":"In vivo activation of antigen-specific CD4 T cells","volume":"19","author":"Jenkins","year":"2001","journal-title":"Annu Rev Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1127470","article-title":"Antigen-specificity measurements are the key to understanding T cell responses","volume":"14","author":"Tippalagama","year":"2023","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387664-5.00003-0","article-title":"The control of adaptive immune responses by the innate immune system","volume":"109","author":"D","year":"2011","journal-title":"Adv Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00486-7","article-title":"Bystander CD4+ T cells: crossroads between innate and adaptive immunity","volume":"52","author":"Lee","year":"2020","journal-title":"Exp Mol Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00791-0","article-title":"Translating B cell immunology to the treatment of antibody-mediated allograft rejection","volume":"20","author":"Heeger","year":"2024","journal-title":"Nat Rev Nephrol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/ajt.15844","article-title":"Mechanisms of organ transplant injury mediated by B cells and antibodies: Implications for antibody-mediated rejection","volume":"20","author":"Chong","year":"2020","journal-title":"Am J Transplant"},{"key":"B25","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41392-021-00823-w","article-title":"T cell receptor (TCR) signaling in health and disease","volume":"6","author":"Shah","year":"2021","journal-title":"Signal Transduction Targeted Ther"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1097\/TP.0000000000004572","article-title":"An immune atlas of T cells in transplant rejection: pathways and therapeutic opportunities","volume":"107","author":"Short","year":"2023","journal-title":"Transplantation"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028533","article-title":"Chronic rejection of cardiac allografts is associated with increased lymphatic flow and cellular trafficking","volume":"137","author":"Edwards","year":"2018","journal-title":"Circulation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1146\/annurev-bioeng-110315-020137","article-title":"Immune tolerance for autoimmune disease and cell transplantation","volume":"18","author":"Luo","year":"2016","journal-title":"Annu Rev BioMed Eng"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1056\/NEJMra1911109","article-title":"Tolerance in the age of immunotherapy","volume":"383","author":"Bluestone","year":"2020","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.44","article-title":"Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance","volume":"12","author":"Zeng","year":"2015","journal-title":"Cell Mol Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1910281116","article-title":"Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity","volume":"116","author":"Badamia","year":"2019","journal-title":"Proc Natl Acad Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adh0085","article-title":"Targeted depletion of PD-1-expressing cells induces immune tolerance through peripheral clonal deletion","volume":"9","author":"C","year":"2024","journal-title":"Sci Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00454-2","article-title":"Rethinking peripheral T cell tolerance: checkpoints across a T cell\u2019s journey","volume":"21","author":"ElTanbouly","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12943-020-01234-1","article-title":"Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects","volume":"19","author":"Li","year":"2020","journal-title":"Mol Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.04.015","article-title":"Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation","volume":"25","author":"Mempel","year":"2006","journal-title":"Immunity"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"B37","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nri821","article-title":"CD4+CD25+ suppressor T cells: more questions than answers","volume":"2","author":"Shevach","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2020.100070","article-title":"Breakdown of T-cell ignorance: the tolerance failure responsible for mainstream autoimmune diseases","volume":"3","author":"Salaman","year":"2020","journal-title":"J Transl Autoimmun"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906026116","article-title":"Immunological ignorance is an enabling feature of the oligo-clonal T cell response to melanoma neoantigens","volume":"116","author":"Linette","year":"2019","journal-title":"Proc Natl Acad Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1029737","article-title":"The dual role of the CD95 and CD95L signaling pathway in glioblastoma","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s41419-022-04688-x","article-title":"Therapeutic approaches targeting CD95L\/CD95 signaling in cancer and autoimmune diseases","volume":"13","author":"Risso","year":"2022","journal-title":"Cell Death Dis"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.05.006","article-title":"Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model","volume":"47","author":"Schleich","year":"2012","journal-title":"Mol Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3260001","article-title":"Caspases: the executioners of apoptosis","volume":"326","author":"Cohen","year":"1997","journal-title":"Biochem J"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061809-121639","article-title":"Caspase substrates and cellular remodeling","volume":"80","author":"Crawford","year":"2011","journal-title":"Annu Rev Biochem"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202201159","article-title":"Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis","volume":"221","author":"Eskandari","year":"2022","journal-title":"J Cell Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations*","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu Rev Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032696","article-title":"CD4 T-cell subsets and the pathophysiology of inflammatory bowel disease","volume":"24","author":"Gomez-Bris","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.12703\/r\/10-30","article-title":"Recent advances in understanding the Th1\/Th2 effector choice","volume":"10","author":"Butcher","year":"2021","journal-title":"Fac Rev"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.761448","article-title":"T cell subsets in graft versus host disease and graft versus tumor","volume":"12","author":"Jiang","year":"2021","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.01.026","article-title":"Delivery strategies to control inflammatory response: modulating M1\u2013M2 polarization in tissue engineering applications","volume":"240","author":"Alvarez","year":"2016","journal-title":"J Controlled Release"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.01.014","article-title":"Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis","volume":"24","author":"Murphy","year":"2010","journal-title":"Brain Behavior Immun"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053352","article-title":"Signaling and function of interleukin-2 in T lymphocytes","volume":"36","author":"Ross","year":"2018","journal-title":"Annu Rev Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01142","article-title":"T cells in fibrosis and fibrotic diseases","volume":"11","author":"Zhang","year":"2020","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/nri1412","article-title":"Fibrotic disease and the TH1\/TH2 paradigm","volume":"4","author":"Wynn","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01382-6","article-title":"The role of interferon-\u03b3 in cardiovascular disease: an update","volume":"69","author":"Elyasi","year":"2020","journal-title":"Inflammation Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161791","article-title":"Th1 effector T cells selectively orchestrate cardiac fibrosis in nonischemic heart failure","volume":"214","author":"Nevers","year":"2017","journal-title":"J Exp Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01009-w","article-title":"Repositioning TH cell polarization from single cytokines to complex help","volume":"22","author":"Tuzlak","year":"2021","journal-title":"Nat Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811702116","article-title":"Hypoxia-inducible factors in CD4+ T cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity","volume":"116","author":"Cho","year":"2019","journal-title":"Proc Natl Acad Sci"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-021-08898-7","article-title":"The therapeutic strategies for SLE by targeting anti-dsDNA antibodies","volume":"63","author":"Wang","year":"2022","journal-title":"Clinic Rev Allerg Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.118","article-title":"TH2 cell development and function","volume":"18","author":"Walker","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.945063","article-title":"Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis","volume":"13","author":"Kokubo","year":"2022","journal-title":"Front Immunol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/j.1600-065X.2011.01004.x","article-title":"T-cell tolerance and the multi-functional role of IL-2R signaling in T-regulatory cells","volume":"241","author":"Cheng","year":"2011","journal-title":"Immunol Rev"},{"key":"B63","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/9781119633884.ch8","article-title":"HLA and antigen receptor biology","volume-title":"Textbook of Transplantation and Mechanical Support for End-stage Heart and Lung Disease","author":"Bery","year":"2023"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1186\/2047-1440-2-16","article-title":"IL-13 signaling via IL-13R\u03b12 triggers TGF-\u03b21-dependent allograft fibrosis","volume":"2","author":"Brunner","year":"2013","journal-title":"Transplant Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0192","article-title":"IL-13 production by donor T cells is prognostic of acute graft-versus-host disease following unrelated donor stem cell transplantation","volume":"103","author":"Jordan","year":"2004","journal-title":"Blood"},{"key":"B66","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41590-022-01387-9","article-title":"TH17 cell heterogeneity and its role in tissue inflammation","volume":"24","author":"Schnell","year":"2023","journal-title":"Nat Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor ROR\u03b3t directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.703972","article-title":"Targeting mitochondrial-derived reactive oxygen species in T cell-mediated autoimmune diseases","volume":"12","author":"Ch\u00e1vez","year":"2021","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201899429","article-title":"Targeting prohibitins at the cell surface prevents Th17\u2010mediated autoimmunity","volume":"37","author":"Buehler","year":"2018","journal-title":"EMBO J"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1279837","article-title":"Interactions between neutrophils and T-helper 17 cells","volume":"14","author":"Fan","year":"2023","journal-title":"Front Immunol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.cytogfr.2022.07.005","article-title":"The involvement of TH17 cells in the pathogenesis of IBD","volume":"69","author":"Jiang","year":"2023","journal-title":"Cytokine Growth Factor Rev"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221751","article-title":"Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis","volume":"220","author":"Kim","year":"2023","journal-title":"J Exp Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1104943","article-title":"The role of Th17 cells in endocrine organs: Involvement of the gut, adipose tissue, liver and bone","volume":"13","author":"Zi","year":"2023","journal-title":"Front Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.immuni.2019.05.004","article-title":"The intestine harbors functionally distinct homeostatic tissue-resident and inflammatory Th17 cells","volume":"51","author":"Omenetti","year":"2019","journal-title":"Immunity"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/frtra.2024.1336563","article-title":"Pretransplant, Th17 dominant alloreactivity in highly sensitized kidney transplant candidates","volume":"3","author":"Negi","year":"2024","journal-title":"Front Transplant"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902999","article-title":"Intragraft Th17 infiltrate promotes lymphoid neogenesis and hastens clinical chronic rejection","volume":"184","author":"Deteix","year":"2010","journal-title":"J Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13304","article-title":"Th-17 alloimmune responses in renal allograft biopsies from recipients of kidney transplants using extended criteria donors during acute T cell\u2013mediated rejection","volume":"15","author":"Matignon","year":"2015","journal-title":"Am J Transplant"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13140","article-title":"IL-17 deficiency attenuates allograft injury and prolongs survival in a murine model of fully MHC-mismatched renal allograft transplantation","volume":"15","author":"Kwan","year":"2015","journal-title":"Am J Transplant"},{"key":"B79","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s12974-022-02446-6","article-title":"The role of Th17 cells\/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A","volume":"19","author":"Fu","year":"2022","journal-title":"J Neuroinflamm"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2011.10.001","article-title":"The IL-17 differentiation pathway and its role in transplant outcome","volume":"18","author":"Serody","year":"2012","journal-title":"Biol Blood Marrow Transplant"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16283","article-title":"Rejection of intestinal allotransplants is driven by memory T helper type 17 immunity and responds to infliximab","volume":"21","author":"Kroemer","year":"2021","journal-title":"Am J Transplant"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/nature04753","article-title":"Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells","volume":"441","author":"Bettelli","year":"2006","journal-title":"Nature"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.01.001","article-title":"TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells","volume":"24","author":"Veldhoen","year":"2006","journal-title":"Immunity"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/nature04754","article-title":"Transforming growth factor-beta induces development of the T(H)17 lineage","volume":"441","author":"Mangan","year":"2006","journal-title":"Nature"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14228","article-title":"Assessment of tocilizumab (anti-interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients","volume":"17","author":"Choi","year":"2017","journal-title":"Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxaa032","article-title":"Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier","volume":"32","author":"Takada","year":"2020","journal-title":"Int Immunol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1681\/ASN.2020071106","article-title":"A randomized clinical trial of anti\u2013IL-6 antibody clazakizumab in late antibody-mediated kidney transplant rejection","volume":"32","author":"Doberer","year":"2021","journal-title":"J Am Soc Nephrol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2016.53","article-title":"The CD8 T-cell response during tolerance induction in liver transplantation","volume":"5","author":"Wong","year":"2016","journal-title":"Clin Transl Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.01.001","article-title":"The many roles of FAS receptor signaling in the immune system","volume":"30","author":"Strasser","year":"2009","journal-title":"Immunity"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141548","article-title":"Effector and memory CTL differentiation","volume":"25","author":"Williams","year":"2007","journal-title":"Annu Rev Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2005.04.007","article-title":"Does programmed CTL proliferation optimize virus control","volume":"26","author":"Wodarz","year":"2005","journal-title":"Trends Immunol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1097\/TP.0b013e318270f3c0","article-title":"Cytotoxic effector function of CD4-independent, CD8+ T cells is mediated by TNF-\u03b1\/TNFR","volume":"94","author":"Zimmerer","year":"2012","journal-title":"Transplantation"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12146","article-title":"Inflammatory triggers of acute rejection of organ allografts","volume":"258","author":"Mori","year":"2014","journal-title":"Immunol Rev"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.921212","article-title":"Human hepatic CD56bright NK cells display a tissue-resident transcriptional profile and enhanced ability to kill allogenic CD8+ T cells","volume":"13","author":"Jameson","year":"2022","journal-title":"Front Immunol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1097\/00007890-200103270-00017","article-title":"Rapid decreases in donor-specific cytotoxic t lymphocyte precursor frequencies and graft outcome after liver and lung transplantation 1","volume":"71","author":"de Haan","year":"2001","journal-title":"Transplantation"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-629006","article-title":"NKG2D expression by CD8+ T cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT","volume":"125","author":"Karimi","year":"2015","journal-title":"Blood"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91138","article-title":"PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells","volume":"127","author":"Ni","year":"2017","journal-title":"J Clin Invest"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12163","article-title":"The importance of regulatory T-cell heterogeneity in maintaining self-tolerance","volume":"259","author":"Yuan","year":"2014","journal-title":"Immunol Rev"},{"key":"B99","article-title":"TGF-\u03b2 function in immune suppression","volume-title":"Negative Co-receptors and Ligands","author":"Yoshimura","year":"2011"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3099","article-title":"IL-1 signaling modulates activation of STAT transcription factors to antagonize retinoic acid signaling and control the TH17 cell\u2013iTreg cell balance","volume":"16","author":"Basu","year":"2015","journal-title":"Nat Immunol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66375","article-title":"Dynamic treg interactions with intratumoral APCs promote local CTL dysfunction","volume":"124","author":"Bauer","year":"2014","journal-title":"J Clin Invest"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12909","article-title":"Treg therapy in transplantation: a general overview","volume":"30","author":"Romano","year":"2017","journal-title":"Transplant Int"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.969633","article-title":"Costimulation blockade and tregs in solid organ transplantation","volume":"13","author":"Muckenhuber","year":"2022","journal-title":"Front Immunol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90598","article-title":"Transplant trials with tregs: perils and promises","volume":"127","author":"Tang","year":"2017","journal-title":"J Clin Invest"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160620","article-title":"Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy","volume":"214","author":"Chen","year":"2017","journal-title":"J Exp Med"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2023.103057","article-title":"Supraphysiological FOXP3 expression in human CAR-tregs results in improved stability, efficacy, and safety of CAR-treg products for clinical application","volume":"138","author":"Henschel","year":"2023","journal-title":"J Autoimmun"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.75","article-title":"The regulation of immune tolerance by FOXP3","volume":"17","author":"Lu","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B108","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/imr.12170","article-title":"Regulatory T-cell homeostasis: steady-state maintenance and modulation during inflammation","volume":"259","author":"Smigiel","year":"2014","journal-title":"Immunol Rev"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15700","article-title":"Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation","volume":"20","author":"S\u00e1nchez-Fueyo","year":"2020","journal-title":"Am J Transplant"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.01.030","article-title":"Liver transplantation immunology: immunosuppression, rejection, and immunomodulation","volume":"78","author":"Burra","year":"2023","journal-title":"J Hepatol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.719954","article-title":"Regulatory T-cell therapy in liver transplantation and chronic liver disease","volume":"12","author":"Hann","year":"2021","journal-title":"Front Immunol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.444","article-title":"Role of the immune system in liver transplantation and its implications for therapeutic interventions","volume":"4","author":"Chen","year":"2023","journal-title":"Medcomm"},{"key":"B113","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1097\/01.tp.0000229473.95202.50","article-title":"Calcineurin inhibitors, but not rapamycin, reduce percentages of CD4+CD25+FOXP3+ regulatory T cells in renal transplant recipients","volume":"82","author":"Segundo","year":"2006","journal-title":"Transplantation"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04269.x","article-title":"Differing effects of rapamycin or calcineurin inhibitor on T-regulatory cells in pediatric liver and kidney transplant recipients","volume":"12","author":"Akimova","year":"2012","journal-title":"Am J Transplant"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.11.043","article-title":"Treatment with rapamycin can restore regulatory T-cell function in IPEX patients","volume":"145","author":"Passerini","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1097\/TP.0000000000001690","article-title":"mTOR inhibition and clinical transplantation: liver","volume":"102","author":"Nashan","year":"2018","journal-title":"Transplantation"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000717","article-title":"Differential effects of calcineurin and mammalian target of rapamycin inhibitors on alloreactive Th1, Th17, and regulatory T cells","volume":"99","author":"Gallon","year":"2015","journal-title":"Transplantation"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048875","article-title":"Advances in liver transplantation: where are we in the pursuit of transplantation tolerance","volume":"51","author":"Safinia","year":"2021","journal-title":"Eur J Immunol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2023.103114","article-title":"The gut ecosystem and immune tolerance","volume":"141","author":"Shao","year":"2023","journal-title":"J Autoimmun"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12801","article-title":"The emerging role of regulatory T cells following lung transplantation","volume":"292","author":"Gauthier","year":"2019","journal-title":"Immunol Rev"},{"key":"B121","doi-asserted-by":"publisher","first-page":"220060","DOI":"10.1183\/16000617.0060-2022","article-title":"Immune processes in the pathogenesis of chronic lung allograft dysfunction: identifying the missing pieces of the puzzle","volume":"31","author":"Bos","year":"2022","journal-title":"Eur Respir Rev"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.06.005","article-title":"Specific gut commensal flora locally alters T cell tuning to endogenous ligands","volume":"38","author":"Chappert","year":"2013","journal-title":"Immunity"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210301","article-title":"Current status regarding immunosuppressive treatment in patients after renal transplantation","volume":"24","author":"Szumilas","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.15040920","article-title":"Long-term immunosuppression management: opportunities and uncertainties","volume":"16","author":"Wojciechowski","year":"2021","journal-title":"Clin J Am Soc Nephrol CJASN"},{"key":"B125","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD008842.pub2","article-title":"Immunosuppressive T\u2010cell antibody induction for heart transplant recipients","author":"Penninga","year":"2013"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1038\/nri1349","article-title":"Co-inhibitory molecules of the B7\u2013CD28 family in the control of T-cell immunity","volume":"4","author":"Chen","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad117","article-title":"Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients","volume":"44","author":"Mahmood","year":"2023","journal-title":"Eur Heart J"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0594","article-title":"CAR T cells produced in vivo to treat cardiac injury","volume":"375","author":"Rurik","year":"2022","journal-title":"Science"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02548","article-title":"T cell allorecognition pathways in solid organ transplantation","volume":"9","author":"Siu","year":"2018","journal-title":"Front Immunol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.158","article-title":"Chronic lymphedema in renal transplant recipients under immunosuppression with sirolimus: presentation of 2 cases","volume":"150","author":"Baliu","year":"2014","journal-title":"JAMA Dermatol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00380-1","article-title":"Immunosuppression for immune-related adverse events during checkpoint inhibition: an intricate balance","volume":"7","author":"Verheijden","year":"2023","journal-title":"NPJ Precis Oncol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-006921","article-title":"Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment","volume":"11","author":"Chiorazzi","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B133","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.eclinm.2025.103300","article-title":"Advocating for the recognition of underlying immunosuppression in critical illness","volume":"85","author":"Martin-Loeches","year":"2025","journal-title":"eClinicalMedicine"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2007.07.017","article-title":"Innate and adaptive immune response to apoptotic cells","volume":"29","author":"Peng","year":"2007","journal-title":"J Autoimmun"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.10.005","article-title":"Innate immune-responses and their role in driving autoimmunity","volume":"18","author":"Toubi","year":"2019","journal-title":"Autoimmun Rev"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1654741","article-title":"Spatial transcriptomics reveals distinct role of monocytes\/macrophages with high FCGR3A expression in kidney transplant rejections","volume":"16","author":"Chen Wongworawat","year":"2025","journal-title":"Front Immunol"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adm8841","article-title":"Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection","volume":"10","author":"Barbetta","year":"2024","journal-title":"Sci Adv"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2022.102822","article-title":"Manufacturing next-generation regulatory T-cell therapies","volume":"78","author":"MacDonald","year":"2022","journal-title":"Curr Opin Biotechnol"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay6422","article-title":"Gene editing to induce FOXP3 expression in human CD4+ T cells leads to a stable regulatory phenotype and function","volume":"12","author":"Honaker","year":"2020","journal-title":"Sci Transl Med"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202310168","article-title":"In situ reprogramming of immune cells using synthetic nanomaterials","volume":"36","author":"Nie","year":"2024","journal-title":"Adv Mater"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1787579\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:19:02Z","timestamp":1774502342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1787579\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":140,"alternative-id":["10.3389\/fimmu.2026.1787579"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1787579","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"article-number":"1787579"}}