{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:57:56Z","timestamp":1772553476707,"version":"3.50.1"},"reference-count":10,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270970"],"award-info":[{"award-number":["32270970"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82241220"],"award-info":[{"award-number":["82241220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019065","name":"Tianjin Municipal Science and Technology Program","doi-asserted-by":"publisher","award":["22JCYBJC00440"],"award-info":[{"award-number":["22JCYBJC00440"]}],"id":[{"id":"10.13039\/501100019065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019065","name":"Tianjin Municipal Science and Technology Program","doi-asserted-by":"publisher","award":["23JCZXJC00360"],"award-info":[{"award-number":["23JCZXJC00360"]}],"id":[{"id":"10.13039\/501100019065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019065","name":"Tianjin Municipal Science and Technology Program","doi-asserted-by":"publisher","award":["24ZXZSSS00030"],"award-info":[{"award-number":["24ZXZSSS00030"]}],"id":[{"id":"10.13039\/501100019065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>T cell-mediated immune response is the center of adaptive immunity. Despite more than five decades of research, the knowledge of mechanisms drives the initiation of T cell-mediated immune response is still limited due to the complexity of T cell-mediated immunity. Based on the accumulating evidences of Th1-mediated immune response, a \u201cpriming-activation\u201d model was proposed to describe the initiation of the immune response. In this model, na\u00efve CD4 T\u00a0cells undergo a priming phase in the draining lymph nodes (dLNs) to polarize to Th1 fate by signals from dendritic cells (DCs). The primed Th1 cells then migrate to the antigen-affected loci and encounter antigen presenting cells (APCs) again. With signals from these cells, the primed Th1 cells differentiate to activated effector cells to coordinate Th1-centered immunity, which is the activation phase of Th1-mediated immune response. Recently, a model for the initiation of Th2-mediated immunity has been proposed, which highly resembles the priming-activation model for Th1 cells. We summarize the advances of Th17-mediated immunity and our understanding of it, and propose a two-step model for the initiation of Th17-mediated autoimmune immunity. Our model is similar to the priming-activation model of Th1 cells, as well. Although there are major knowledge gaps on molecular and cellular mechanisms in our model to be addressed, we hope that this model, with the associated gaps being addressed, will provide framework for research on the initiation of Th17-mediated immune responses and eventually enhances our understanding of how T cell-mediated immunity initiates.<\/jats:p>","DOI":"10.1515\/mr-2025-0066","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:58:15Z","timestamp":1768831095000},"page":"83-86","source":"Crossref","is-referenced-by-count":0,"title":["Modes of the initiation of T cell-mediated immune responses"],"prefix":"10.1515","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-9307","authenticated-orcid":false,"given":"Long","family":"Li","sequence":"first","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Cellular and Molecular Immunology , Department of Immunology, Tianjin Medical University , Tianjin , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Yao","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Cellular and Molecular Immunology , Department of Immunology, Tianjin Medical University , Tianjin , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"2026030313001870989_j_mr-2025-0066_ref_001","unstructured":"Janeway, JC. The priming of helper T\u00a0cells. Semin Immunol 1989;1:13\u201320."},{"key":"2026030313001870989_j_mr-2025-0066_ref_002","doi-asserted-by":"crossref","unstructured":"Annunziato, F, Romagnani, C, Romagnani, S. The 3 major types of innate and adaptive cell-mediated effector immunity. J\u00a0Allergy Clin Immunol 2015;135:626\u201335. https:\/\/doi.org\/10.1016\/j.jaci.2014.11.001.","DOI":"10.1016\/j.jaci.2014.11.001"},{"key":"2026030313001870989_j_mr-2025-0066_ref_003","doi-asserted-by":"crossref","unstructured":"Chandra, P, Grigsby, SJ, Philips, JA. Immune evasion and provocation by Mycobacterium tuberculosis. Nat Rev Microbiol 2022;20:750\u201366. https:\/\/doi.org\/10.1038\/s41579-022-00763-4.","DOI":"10.1038\/s41579-022-00763-4"},{"key":"2026030313001870989_j_mr-2025-0066_ref_004","doi-asserted-by":"crossref","unstructured":"Gearty, SV, D\u00fcndar, F, Zumbo, P, Espinosa-Carrasco, G, Shakiba, M, Sanchez-Rivera, FJ, et al.. An autoimmune stem-like CD8 T\u00a0cell population drives type 1 diabetes. Nature 2022;602:156\u201361. https:\/\/doi.org\/10.1038\/s41586-021-04248-x.","DOI":"10.1038\/s41586-021-04248-x"},{"key":"2026030313001870989_j_mr-2025-0066_ref_005","doi-asserted-by":"crossref","unstructured":"Prokhnevska, N, Cardenas, MA, Valanparambil, RM, Sobierajska, E, Barwick, BG, Jansen, C, et al.. CD8+ T\u00a0cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor. Immunity 2023;56:107\u201324. https:\/\/doi.org\/10.1016\/j.immuni.2022.12.002.","DOI":"10.1016\/j.immuni.2022.12.002"},{"key":"2026030313001870989_j_mr-2025-0066_ref_006","doi-asserted-by":"crossref","unstructured":"Kopp, EB, Agaronyan, K, Licona-Lim\u00f3n, I, Nish, SA, Medzhitov, R. Modes of type 2 immune response initiation. Immunity 2023;56:687\u201394. https:\/\/doi.org\/10.1016\/j.immuni.2023.03.015.","DOI":"10.1016\/j.immuni.2023.03.015"},{"key":"2026030313001870989_j_mr-2025-0066_ref_007","doi-asserted-by":"crossref","unstructured":"Schnell, A, Littman, DR, Kuchroo, VK. Th17 cell heterogeneity and its role in tissue inflammation. Nat Immunol 2023;24:19\u201329. https:\/\/doi.org\/10.1038\/s41590-022-01387-9.","DOI":"10.1038\/s41590-022-01387-9"},{"key":"2026030313001870989_j_mr-2025-0066_ref_008","doi-asserted-by":"crossref","unstructured":"Lee, Y, Awasthi, A, Yosef, N, Quintana, FJ, Xiao, S, Peters, A, et al.. Induction and molecular signature of pathogenic Th17 cells. Nat Immunol 2012;13:991\u20139. https:\/\/doi.org\/10.1038\/ni.2416.","DOI":"10.1038\/ni.2416"},{"key":"2026030313001870989_j_mr-2025-0066_ref_009","doi-asserted-by":"crossref","unstructured":"Mangani, D, Subramanian, A, Huang, L, Cheng, H, Krovi, SH, Wu, Y, et al.. Transcription factor TCF1 binds to ROR\u03b3t and orchestrates a regulatory network that determines homeostatic Th17 cell state. Immunity 2024;57:2565\u201382.e6. https:\/\/doi.org\/10.1016\/j.immuni.2024.09.017.","DOI":"10.1016\/j.immuni.2024.09.017"},{"key":"2026030313001870989_j_mr-2025-0066_ref_010","doi-asserted-by":"crossref","unstructured":"Hall, JA, Pokrovskii, M, Kroehling, L, Kim, B-R, Kim, SY, Wu, L, et al.. Transcription factor ROR\u03b1 enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element. Immunity 2022;55:2027\u201343.e9. https:\/\/doi.org\/10.1016\/j.immuni.2022.09.013.","DOI":"10.1016\/j.immuni.2022.09.013"}],"container-title":["Medical Review"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/mr-2025-0066\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/mr-2025-0066\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T13:05:03Z","timestamp":1772543103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/mr-2025-0066\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3,4]]},"published-print":{"date-parts":[[2026,3,4]]}},"alternative-id":["10.1515\/mr-2025-0066"],"URL":"https:\/\/doi.org\/10.1515\/mr-2025-0066","relation":{},"ISSN":["2749-9642"],"issn-type":[{"value":"2749-9642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}