{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:30:59Z","timestamp":1760711459928,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T00:00:00Z","timestamp":1735948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Mexicano del Seguro Social","award":["R-2018-785-074","R-2023-785-028"],"award-info":[{"award-number":["R-2018-785-074","R-2023-785-028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Type 1 diabetes (T1D) is a complex disease driven by the immune system attacking the insulin-producing beta cells in the pancreas. Understanding the role of different T cell subpopulations in the development and progression of T1D is crucial. By employing flow cytometry to compare the characteristics of T cells, we can pinpoint potential indicators of treatment response or therapeutic inefficacy. Our study reveals elevated prolactin (PRL) levels in T1D patients, along with a decreased production of key cytokines. Additionally, PD1 appears to play a significant role in T1D. Notably, PRL levels correlate with an earlier disease onset and a specific T cell phenotype, hinting at the potential influence of PRL. These findings highlight the need for further research to identify promising cellular targets for more effective and tailored therapies.<\/jats:p>","DOI":"10.3390\/cells14010048","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T09:17:02Z","timestamp":1736155022000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating T Cell Subsets in Type 1 Diabetes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5159-9856","authenticated-orcid":false,"given":"Aldo","family":"Ferreira-Hermosillo","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Enfermedades End\u00f3crinas de la UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Santana-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, de la UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Vaquero-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, de la UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-0383","authenticated-orcid":false,"given":"Manuel R.","family":"Garc\u00eda-S\u00e1enz","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, de la UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8028-313X","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Castro-R\u00edos","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Epidemiolog\u00eda Cl\u00ednica de la UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-946X","authenticated-orcid":false,"given":"Adriana K.","family":"Ch\u00e1vez-Rueda","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, de la UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita A.","family":"G\u00f3mez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Epidemiolog\u00eda Cl\u00ednica de la UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Ch\u00e1vez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, de la UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4213-4659","authenticated-orcid":false,"given":"Mar\u00eda V.","family":"Legorreta-Haquet","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, de la UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,4]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2021). IDF Diabetes Atlas, International Diabetes Federation. [10th ed.]."},{"key":"ref_2","first-page":"738","article-title":"Predictors of increasing BMI during the course of diabetes in children and adolescents with type 1 diabetes: Data from the German\/Austrian DPV multicentre survey","volume":"9","author":"Rosenbauer","year":"2014","journal-title":"Arch. Dis. Child."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2337\/dc16-1625","article-title":"Longitudinal Trajectories of Metabolic Control From Childhood to Young Adulthood in Type 1 Diabetes From a Large German\/Austrian Registry: A Group-Based Modeling Approach","volume":"40","author":"Schwandt","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4103\/ijem.IJEM_550_17","article-title":"Premarriage Counseling in Type 1 Diabetes","volume":"22","author":"Priya","year":"2018","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/S0140-6736(18)31320-5","article-title":"Type 1 diabetes","volume":"391","author":"DiMeglio","year":"2018","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1007\/s00125-022-05778-3","article-title":"Precision medicine in type 1 diabetes","volume":"65","author":"Carr","year":"2022","journal-title":"Diabetologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11892-021-01384-6","article-title":"The role of programmed death-1 in type 1 diabetes","volume":"21","author":"Tucker","year":"2021","journal-title":"Curr. Diab Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1084\/jem.192.7.1027","article-title":"Engagement of the PD-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation","volume":"192","author":"Freeman","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nri.2017.108","article-title":"The diverse functions of the PD1 inhibitory pathway","volume":"18","author":"Sharpe","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51936","DOI":"10.18632\/oncotarget.17232","article-title":"PD1 signal transduction pathways in T cells","volume":"8","author":"Arasanz","year":"2017","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11823","DOI":"10.1073\/pnas.0505497102","article-title":"Establishment of NOD-Pdcd1\u2212\/\u2212 mice as an efficient animal model of type I diabetes","volume":"102","author":"Wang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00439-006-0309-8","article-title":"PD-1 gene haplotype is associated with the development of type 1 diabetes mellitus in Japanese children","volume":"121","author":"Ni","year":"2007","journal-title":"Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/dmrr.2552","article-title":"PD-L1 gene polymorphisms and low serum level ofPD-L1 protein are associated to type 1 diabetes in Chile","volume":"30","author":"Pizarro","year":"2014","journal-title":"Diabetes\/Metab. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1046\/j.1399-0039.2003.00136.x","article-title":"Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes","volume":"62","author":"Nielsen","year":"2003","journal-title":"Tissue Antigens"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/ni.1877","article-title":"PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells","volume":"11","author":"Szumilas","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.immuni.2018.06.012","article-title":"PD-1 Controls Follicular T Helper Cell Positioning and Function","volume":"49","author":"Shi","year":"2018","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1084\/jem.20061800","article-title":"Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade","volume":"203","author":"Freeman","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","article-title":"T follicular helper cell biology: A decade of discovery and diseases","volume":"50","author":"Crotty","year":"2019","journal-title":"Immunity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5556","DOI":"10.4049\/jimmunol.1002828","article-title":"CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses","volume":"186","author":"Chevalier","year":"2011","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1172\/JCI76238","article-title":"Follicular helper T cell signature in type 1 diabetes","volume":"125","author":"Kenefeck","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E6659","DOI":"10.1073\/pnas.1606646113","article-title":"miRNA92a targets KLF2 and the phosphatase PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity","volume":"113","author":"Serr","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"437","DOI":"10.2337\/db16-0714","article-title":"Circulating CXCR5+PD-1+ICOS+ Follicular T Helper Cells Are Increased Close to the Diagnosis of Type 1 Diabetes in Children With Multiple Autoantibodies","volume":"66","author":"Viisanen","year":"2017","journal-title":"Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/imcb.12444","article-title":"Harnessing CD8+T-cell exhaustion to treat type 1 diabetes","volume":"99","author":"Kwong","year":"2021","journal-title":"Immunol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nm.4241","article-title":"T memory stem cells in health and disease","volume":"23","author":"Gattinoni","year":"2017","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s13238-020-00707-9","article-title":"Memory T cells: Strategies for optimizing tumor immunotherapy","volume":"11","author":"Liu","year":"2020","journal-title":"Protein Cell"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ramirez-Hernandez, G., Adan-Castro, E., Diaz-Lezama, N., Ruiz-Herrera, X., de la Escalera, G.M., Macotela, Y., and Clapp, C. (2021). Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.619696"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Legorreta-Haquet, M.V., Santana-S\u00e1nchez, P., Ch\u00e1vez-S\u00e1nchez, L., and Ch\u00e1vez-Rueda, A.K. (2022). The effect of prolactin on immune cell subsets involved in SLE pathogenesis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1016427"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1210\/en.2015-1549","article-title":"Prolactin as an Adjunct for Type 1 Diabetes Immunotherapy","volume":"157","author":"Hyslop","year":"2016","journal-title":"Endocrinology"},{"key":"ref_29","unstructured":"American Boardof Internal Medicine (2024). ABIM Laboratory Test Reference Ranges\u2013January 2024, American Boardof Internal Medicine."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"BMI-S38440","DOI":"10.4137\/BMI.S38440","article-title":"Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients","volume":"11","author":"Sherwani","year":"2016","journal-title":"Biomark. Insights"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109038","DOI":"10.1016\/j.diabres.2021.109038","article-title":"Glycemic control, treatment and complications in patients with type 1 diabetes amongst healthcare settings in Mexico","volume":"180","year":"2021","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"A465","DOI":"10.1016\/j.autrev.2011.11.009","article-title":"Prolactin and autoimmunity","volume":"11","author":"Shelly","year":"2012","journal-title":"Autoimmun. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.clim.2005.03.013","article-title":"Identification of prolactin as a novel immunomodulator on the expression of co-stimulatory molecules and cytokine secretions on T and B human lymphocytes","volume":"116","author":"Chavezrueda","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eaao4013","DOI":"10.1126\/sciimmunol.aao4013","article-title":"Islet-reactive CD8+ T-cell frequencies in the pancreas but not blood distinguish type 1 diabetes from healthy donors","volume":"3","author":"Culina","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1242454","DOI":"10.1126\/science.1242454","article-title":"Fueling Immunity: Insights into Metabolism and Lymphocyte Function","volume":"342","author":"Pearce","year":"2013","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3892\/ijo.2022.5364","article-title":"Treatment of patients with cancer using PD-1\/PD-L1 antibodies: Adverse effects and management strategies (Review)","volume":"60","author":"Sun","year":"2022","journal-title":"Int. J. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.2337\/dc21-2213","article-title":"Immune Checkpoint Inhibitors and Risk of Type 1 Diabetes","volume":"45","author":"Chen","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1097\/CM9.0000000000000972","article-title":"Type 1 diabetes induced by immune checkpoint inhibitors","volume":"133","author":"Zhang","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.jaad.2003.10.679","article-title":"Lesional T cells and dermal dendrocytes in psoriasis plaque express increased levels of granulysin","volume":"51","author":"Jiang","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7474","DOI":"10.4049\/jimmunol.175.11.7474","article-title":"Coordinate expression of CC chemokine ligand 5, granulysin, and perforin in CD8+ T cells provides a host defense mechanism against Mycobacterium tuberculosis","volume":"175","author":"Stegelmann","year":"2005","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/ced.12428","article-title":"Cytotoxic granules in distinct subsets of cutaneous lupus erythematosus","volume":"39","author":"Fogagnolo","year":"2014","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/icb.2015.89","article-title":"Perforin facilitates beta cell killing and regulates autoreactive CD8+ T-cell responses to antigen in mouse models of type 1 diabetes","volume":"94","author":"Trivedi","year":"2016","journal-title":"Immunol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eaai7793","DOI":"10.1126\/sciimmunol.aai7793","article-title":"Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes","volume":"1","author":"Long","year":"2016","journal-title":"Sci. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1210\/endo.132.2.8425500","article-title":"Effect of homologous placental lactogens, prolactins, and growth hormones on islet b-cell division and insulin secretion in rat, mouse, and human islets: Implication for placental lactogen regulation of islet function during pregnancy","volume":"132","author":"Brelje","year":"1993","journal-title":"Endocrinology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1677\/joe.0.1640277","article-title":"Prolactin induction of insulin gene expression: The roles of glucose and glucose transporter-2","volume":"164","author":"Petryk","year":"2000","journal-title":"J. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3904\/kjim.1993.8.1.8","article-title":"Direct relationship between elevated free testosterone and insulin resistance in hyperprolactinemic women","volume":"81","author":"Kim","year":"1993","journal-title":"Korean J. Intern. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1365-2265.1995.tb00541.x","article-title":"Peripheral glucose metabolism in human hyperprolactinaemia","volume":"43","author":"Foss","year":"1995","journal-title":"Clin. Endocrinol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/1\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:22:49Z","timestamp":1759918969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/1\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,4]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cells14010048"],"URL":"https:\/\/doi.org\/10.3390\/cells14010048","relation":{},"ISSN":["2073-4409"],"issn-type":[{"type":"electronic","value":"2073-4409"}],"subject":[],"published":{"date-parts":[[2025,1,4]]}}}