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The key retinal autoantigen in these mice is interphotoreceptor retinoid-binding protein (IRBP). The CD4+ T cells recognizing the dominant epitope of IRBP, called P2, from eye-draining lymph nodes of mice with or without uveitis and from the retinas of mice with uveitis, were characterized by single-cell RNA sequencing (scRNA-seq) and flow cytometry. Mice with uveitis had autoantigen-specific T cells in the eye-draining lymph node and in the retinas, exhibiting a range of activation states and a Th1 polarization, along with a small fraction of Tregs. Mice without uveitis had low numbers of P2-specific T cells in the eye-draining lymph nodes, and in most mice a substantial proportion of them were FoxP3+ Tregs. Transient depletion of Tregs by treatment of heathy AireGW\/+Lyn\u2212\/\u2212 Foxp3DTR+\/Y mice with diphtheria toxin resulted in rapid expansion of P2-specific CD4+ T cells in the eye-draining LN, and some of the Treg depleted mice went on to develop uveitis. Thus, development of inflammation in the retina was limited by a checkpoint in the eye-draining lymph nodes involving Tregs, and also apparently by an additional peripheral tolerogenic mechanism.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf334","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:29:04Z","timestamp":1773822544000},"source":"Crossref","is-referenced-by-count":1,"title":["Immune checkpoints in a genetically engineered mouse model of spontaneous autoimmune uveitis"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5573-8991","authenticated-orcid":false,"given":"Mianmian","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco , San Francisco, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamir 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