{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:18:59Z","timestamp":1790338739688,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI092106"],"award-info":[{"award-number":["R01AI092106"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX003677"],"award-info":[{"award-number":["I01BX003677"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["T32AI007485"],"award-info":[{"award-number":["T32AI007485"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["T32AI007511"],"award-info":[{"award-number":["T32AI007511"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS. We have previously demonstrated that CNS-specific CD8 T cells possess a disease-suppressive function in MS and variations of its animal model, experimental autoimmune encephalomyelitis (EAE), including the highly clinically relevant relapsing-remitting EAE disease course. Regulatory CD8 T cell subsets have been identified in EAE and other autoimmune diseases, but studies vary in defining phenotypic properties of these cells. In relapsing-remitting EAE, PLP178-191 CD8 T cells suppress disease, whereas PLP139-151 CD8 T cells lack this function. In this study, we used this model to delineate the unique phenotypic properties of CNS-specific regulatory PLP178-191 CD8 T cells versus nonregulatory PLP139-151 or OVA323-339 CD8 T cells. Using multiparametric flow cytometric analyses of phenotypic marker expression, we identified a CXCR3+ subpopulation among activated regulatory CD8 T cells, relative to nonregulatory counterparts. This subset exhibited increased degranulation and IFN-\u03b3 and IL-10 coproduction. A similar subset was also identified in C57BL\/6 mice within autoregulatory PLP178-191 CD8 T cells but not within nonregulatory OVA323-339 CD8 T cells. This disease-suppressing CD8 T cell subpopulation provides better insights into functional regulatory mechanisms, and targeted enhancement of this subset could represent a novel immunotherapeutic approach for MS.<\/jats:p>","DOI":"10.4049\/jimmunol.2001143","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T21:27:52Z","timestamp":1612819672000},"page":"1151-1160","source":"Crossref","is-referenced-by-count":8,"title":["A Functionally Distinct CXCR3+\/IFN-\u03b3+\/IL-10+ Subset Defines Disease-Suppressive Myelin-Specific CD8 T Cells"],"prefix":"10.1093","volume":"206","author":[{"given":"Ashley A","family":"Brate","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Iowa Health Care , Iowa City, IA 52241"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52241"},{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3440-7848","authenticated-orcid":false,"given":"Alexander W","family":"Boyden","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa Health Care , Iowa City, IA 52241"},{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3107-3961","authenticated-orcid":false,"given":"Isaac J","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa Health Care , Iowa City, IA 52241"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-2439","authenticated-orcid":false,"given":"Vladimir P","family":"Badovinac","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa Health Care , Iowa City, IA 52241"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52241"},{"name":"Department of Microbiology and Immunology, University of Iowa , Iowa City, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-6950","authenticated-orcid":false,"given":"Nitin J","family":"Karandikar","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa Health Care , Iowa City, IA 52241"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52241"},{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"2025030502022287900_r1","article-title":"The contribution of immune and glial cell types in experimental autoimmune encephalomyelitis and multiple sclerosis","volume":"2014","author":"Duffy","year":"2014","journal-title":"Mult. 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