{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:29:22Z","timestamp":1770413362066,"version":"3.49.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To prevent potentially damaging inflammatory responses, the eye actively promotes local immune tolerance via a variety of mechanisms. Owing to trauma, infection, or other ongoing autoimmunity, these mechanisms sometimes fail, and an autoimmune disorder may develop in the eye. In mice of the C57BL\/10 (B10) background, autoimmune keratitis often develops spontaneously, particularly in the females. Its incidence is greatly elevated in the absence of \u03b3\u03b4 T cells, such that \u223c80% of female B10.TCR\u03b4\u2212\/\u2212 mice develop keratitis by 18 wk of age. In this article, we show that CD8+ \u03b1\u03b2 T cells are the drivers of this disease, because adoptive transfer of CD8+, but not CD4+, T cells to keratitis-resistant B10.TCR\u03b2\/\u03b4\u2212\/\u2212 hosts induced a high incidence of keratitis. This finding was unexpected because in other autoimmune diseases, more often CD4+ \u03b1\u03b2 T cells, or both CD4+ and CD8+ \u03b1\u03b2 T cells, mediate the disease. Compared with wild-type B10 mice, B10.TCR\u03b4\u2212\/\u2212 mice also show increased percentages of peripheral memory phenotype CD8+ \u03b1\u03b2 T cells, along with an elevated frequency of CD8+ \u03b1\u03b2 T cells biased to produce inflammatory cytokines. In addition, B10.TCR\u03b4\u2212\/- mice have fewer peripheral CD4+ CD25+ Foxp3+ \u03b1\u03b2 regulatory T cells (Tregs), which express lower levels of receptors needed for Treg development and function. Together, these observations suggest that in B10 background mice, \u03b3\u03b4 T cells are required to generate adequate numbers of CD4+ CD25+ Foxp3+ Tregs, and that in B10.TCR\u03b4\u2212\/\u2212 mice a Treg deficiency allows dysregulated effector or memory CD8+ \u03b1\u03b2 T cells to infiltrate the cornea and provoke an autoimmune attack.<\/jats:p>","DOI":"10.4049\/jimmunol.1501604","type":"journal-article","created":{"date-parts":[[2015,11,14]],"date-time":"2015-11-14T02:13:19Z","timestamp":1447467199000},"page":"5572-5581","source":"Crossref","is-referenced-by-count":20,"title":["\u03b3\u03b4 T Cell\u2013Dependent Regulatory T Cells Prevent the Development of Autoimmune Keratitis"],"prefix":"10.1093","volume":"195","author":[{"given":"Yafei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biomedical Research, National Jewish Health , Denver, CO 80206"},{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine , Aurora, CO 80045"},{"name":"Joint Laboratory for Stem Cell Engineering and Technology Transfer, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan City 430030 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2400-7488","authenticated-orcid":false,"given":"Zhifang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Jewish Health , Denver, CO 80206"},{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine , Aurora, CO 80045"},{"name":"Department of Breast and Thyroid Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan City 430030 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Jewish Health , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"McGowan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Jewish Health , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Casper","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Jewish Health , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4851-0416","authenticated-orcid":false,"given":"Deming","family":"Sun","sequence":"additional","affiliation":[{"name":"Doheny Eye Institute, Department of Ophthalmology, University of Southern California , Los Angeles, CA 90033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willi K","family":"Born","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Jewish Health , Denver, CO 80206"},{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca L","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Jewish Health , Denver, CO 80206"},{"name":"Department of Immunology and Microbiology, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,12,15]]},"reference":[{"key":"2025030704284563600_r1","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.4049\/jimmunol.166.7.4327","article-title":"\u03b3 \u03b4 T cells are needed for ocular immune privilege and corneal graft survival","volume":"166","author":"Skelsey","year":"2001","journal-title":"J. Immunol."},{"key":"2025030704284563600_r2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1046\/j.1365-2567.2001.01285.x","article-title":"gammadelta T cells are critical for the induction of anterior chamber-associated immune deviation","volume":"104","author":"Xu","year":"2001","journal-title":"Immunology"},{"key":"2025030704284563600_r3","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1084\/jem.185.11.1969","article-title":"T cell receptor-\u03b3\/\u03b4 cells protect mice from herpes simplex virus type 1-induced lethal encephalitis","volume":"185","author":"Sciammas","year":"1997","journal-title":"J. Exp. Med."},{"key":"2025030704284563600_r4","doi-asserted-by":"crossref","first-page":"838","DOI":"10.2353\/ajpath.2007.070008","article-title":"\u03b3 \u03b4 T cells are necessary for platelet and neutrophil accumulation in limbal vessels and efficient epithelial repair after corneal abrasion","volume":"171","author":"Li","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2025030704284563600_r5","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.ajpath.2010.12.001","article-title":"IL-17 and VEGF are necessary for efficient corneal nerve regeneration","volume":"178","author":"Li","year":"2011","journal-title":"Am. J. Pathol."},{"key":"2025030704284563600_r6","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1096\/fj.11-184804","article-title":"CCL20, \u03b3\u03b4 T cells, and IL-22 in corneal epithelial healing","volume":"25","author":"Li","year":"2011","journal-title":"FASEB J."},{"key":"2025030704284563600_r7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nm0308-247","article-title":"Interleukin-22: a sheep in wolf\u2019s clothing","volume":"14","author":"Laurence","year":"2008","journal-title":"Nat. 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Ophthalmol."},{"key":"2025030704284563600_r13","doi-asserted-by":"crossref","first-page":"8331","DOI":"10.4049\/jimmunol.177.12.8331","article-title":"Gammadelta T cells promote anterior chamber-associated immune deviation and immune privilege through their production of IL-10","volume":"177","author":"Ashour","year":"2006","journal-title":"J. Immunol."},{"key":"2025030704284563600_r14","doi-asserted-by":"crossref","first-page":"560","DOI":"10.4049\/jimmunol.0900241","article-title":"Major role of \u03b3 \u03b4 T cells in the generation of IL-17+ uveitogenic T cells","volume":"183","author":"Cui","year":"2009","journal-title":"J. Immunol."},{"key":"2025030704284563600_r15","doi-asserted-by":"crossref","first-page":"5920","DOI":"10.1167\/iovs.10-6758","article-title":"Activated gammadelta T cells promote the activation of uveitogenic T cells and exacerbate EAU development","volume":"52","author":"Nian","year":"2011","journal-title":"Invest. Ophthalmol. Vis. 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Liver Physiol."},{"key":"2025030704284563600_r33","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/ni.3171","article-title":"Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition","volume":"16","author":"Weist","year":"2015","journal-title":"Nat. Immunol."},{"key":"2025030704284563600_r34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0092-8674(93)90112-4","article-title":"T cell receptor \u03b4 gene mutant mice: independent generation of \u03b1 \u03b2 T cells and programmed rearrangements of \u03b3 \u03b4 TCR genes","volume":"72","author":"Itohara","year":"1993","journal-title":"Cell"},{"key":"2025030704284563600_r35","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0145-305X(03)00027-2","article-title":"The mouse (Mus musculus) T cell receptor \u03b1 (TRA) and \u03b4 (TRD) variable genes","volume":"27","author":"Bosc","year":"2003","journal-title":"Dev. Comp. 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