{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:28:07Z","timestamp":1779186487145,"version":"3.51.4"},"reference-count":102,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic \u03b2-cells. Both lymphocytes and various innate immune cells contribute to its immunopathogenesis. Among lymphocytes, in addition to CD8+ T cells, CD4+ T cells, and B cells, growing attention has been directed toward some unconventional T-cell subsets, such as TCR\u03b1\u03b2+ double-negative T (DNT) cells, based on findings in several autoimmune\/rheumatic diseases. This narrative review aims to summarize and analyze the available data on the potential role of DNT cells (and, in detail, the TCR\u03b1\u03b2+ subset) in the immunopathogenesis of autoimmune diabetes\/T1DM. Most of the current knowledge regarding DNT cell homeostasis in this pathological setting derives from experimental models, especially Non-Obese Diabetic (NOD) mice. In murine autoimmune diabetes, TCR\u03b1\u03b2+DNT cells appear to exert a predominantly protective role against immune-mediated \u03b2-cell injury. These cells can be observed in multiple anatomical sites, including the thymus, peripheral blood, secondary lymphoid organs (spleen and lymph nodes) and, under pathological conditions, in non-lymphoid organs, like within the pancreas and, in detail, pancreatic islets, in the setting of autoimmune diabetes. Experimental evidence suggests that TCR\u03b1\u03b2+DNT cells may attenuate the CD8+ T cell-mediated destruction of pancreatic \u03b2-cells, both directly and indirectly, through the inhibition of CD4+ T cells and B cells implicated in this immunopathological process. Unfortunately, very few studies have examined TCR\u03b1\u03b2+DNT cells in patients with T1DM. This important knowledge gap highlights the need for dedicated clinical and translational research to better elucidate the role of TCR\u03b1\u03b2+DNT cells in T1DM, especially given the preliminary findings pointing toward their potential immunoregulatory relevance.<\/jats:p>","DOI":"10.3390\/cells15010058","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:34:23Z","timestamp":1767198863000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["(TCR\u03b1\u03b2+) Double-Negative T Cells in Type 1 Diabetes Mellitus"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-9334","authenticated-orcid":false,"given":"Dimitri","family":"Poddighe","sequence":"first","affiliation":[{"name":"College of Health Sciences, VinUniversity, Vinhomes Ocean Park, Gia Lam, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6666-511X","authenticated-orcid":false,"given":"Assel","family":"Mussayeva","sequence":"additional","affiliation":[{"name":"School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1834-1909","authenticated-orcid":false,"given":"Kuanysh","family":"Dossybayeva","sequence":"additional","affiliation":[{"name":"School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulsamal","family":"Zhubanova","sequence":"additional","affiliation":[{"name":"School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinara","family":"Galiyeva","sequence":"additional","affiliation":[{"name":"School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-9417","authenticated-orcid":false,"given":"Khac Linh","family":"Le","sequence":"additional","affiliation":[{"name":"College of Health Sciences, VinUniversity, Vinhomes Ocean Park, Gia Lam, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1270-1886","authenticated-orcid":false,"given":"Matthew Naanlep","family":"Tanko","sequence":"additional","affiliation":[{"name":"School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","article-title":"Type 1 diabetes","volume":"383","author":"Atkinson","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e70120","DOI":"10.1111\/1753-0407.70120","article-title":"A comprehensive review of novel advances in type 1 diabetes mellitus","volume":"17","author":"Ebrahimpour","year":"2025","journal-title":"J. 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