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A better understanding of how these iatrogenic diseases compare with naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced type 1 diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally exhausted\/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3\u2212 T cells, and a decrease in memory CD4+FoxP3\u2212 and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ.<\/jats:p>","DOI":"10.1084\/jem.20221920","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T02:23:20Z","timestamp":1687573400000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Single-cell profiling reveals unique features of diabetogenic T cells in anti-PD-1-induced type 1 diabetes mice"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-4986","authenticated-orcid":true,"given":"Jenna L.","family":"Collier","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04b6nzv94","id-type":"ROR","asserted-by":"publisher"}],"name":"Blavatnik Institute, Harvard Medical School 1 Department of 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