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As a result, low\u2010affinity T cells are often disregarded as nonantigen\u2010specific cells irrelevant to the immune response. Our study aimed to assess how the level of self\u2010antigen reactivity shapes T\u2010cell lineage and effector responses in the context of spontaneous tissue\u2010specific autoimmunity observed in NOD mice. Using multicolor flow cytometry in combination with Nur77<jats:sup>GFP<\/jats:sup> reporter of TCR signaling, we identified a dormant population of T cells that infiltrated the pancreatic islets of prediabetic NOD mice, which exhibited reduced levels of self\u2010tissue reactivity based on expression of CD5 and Nur77<jats:sup>GFP<\/jats:sup>. We showed that these CD5<jats:sup>low<\/jats:sup> T cells had a unique TCR repertoire and exhibited low activation and minimal effector function; however, induced rapid diabetes upon transfer. The CD4<jats:sup>+<\/jats:sup>CD5<jats:sup>low<\/jats:sup> T\u2010cell population displayed transcriptional signature of central memory T cells, consistent with the ability to acquire effector function post\u2010transfer. Transcriptional profile of CD5<jats:sup>low<\/jats:sup> T cells was similar to T cells expressing a low\u2010affinity TCR, indicating TCR affinity to be an important factor in shaping CD5<jats:sup>low<\/jats:sup> T\u2010cell phenotype and function at the tissue site. Overall, our study suggests that autoimmune tissue can maintain a reservoir of undifferentiated central memory\u2010like autoreactive T cells with pathogenic effector potential that might be an important source for effector T cells during long\u2010term chronic autoimmunity.<\/jats:p>","DOI":"10.1002\/eji.202149690","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T13:10:05Z","timestamp":1649337005000},"page":"1158-1170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A dormant T\u2010cell population with autoimmune potential exhibits low self\u2010reactivity and infiltrates islets in type 1 diabetes"],"prefix":"10.1002","volume":"52","author":[{"given":"Yuelin","family":"Kong","sequence":"first","affiliation":[{"name":"Section of Diabetes and Endocrinology Department of Pediatrics Baylor College of Medicine Texas Children's Hospital  Houston TX 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