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However, the role of GITR stimulation on CD8 T cells and the nature of tumor rejection Ags have yet to be determined. In this study, we show that a stimulatory mAb to GITR (clone DTA-1) acts directly on CD8 T cells, but not on CD4+CD25+ regulatory T (Treg) cells, in B16 tumor-bearing mice to induce concomitant immunity against secondary B16 tumors, as well as protective memory following surgical excision of the primary tumor. Melanoma growth itself induced GITR expression on tumor-specific CD8 T cells, providing a mechanism whereby these cells may respond to stimulatory anti-GITR. Unexpectedly, in contrast to Treg cell depletion therapy with anti-CD4, GITR stimulation induced very weak CD8 T cell responses to melanocyte differentiation Ags expressed by the tumor, and did not induce autoimmune vitiligo. Accordingly, GITR-stimulated hosts that were primed with B16 melanoma rejected B16, but not the unrelated JBRH melanoma, indicating that tumor rejection Ags are tumor-specific rather than shared. In support of this, we show that GITR stimulation induces CD8 T cell responses to a tumor-specific Ag, and that these responses are of higher functional avidity compared with those induced by Treg cell depletion. We conclude that stimulation of GITR on effector CD8 T cells results in high-avidity T cell responses to tumor-specific Ags, thereby inducing potent antitumor immunity in the absence of autoimmunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1001308","type":"journal-article","created":{"date-parts":[[2010,11,25]],"date-time":"2010-11-25T04:10:55Z","timestamp":1290658255000},"page":"275-283","source":"Crossref","is-referenced-by-count":36,"title":["Stimulation of the Glucocorticoid-Induced TNF Receptor Family-Related Receptor on CD8 T Cells Induces Protective and High-Avidity T Cell Responses to Tumor-Specific Antigens"],"prefix":"10.1093","volume":"186","author":[{"given":"Anik L","family":"C\u00f4t\u00e9","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School, Norris Cotton Cancer Center , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peisheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School, Norris Cotton Cancer Center , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago , Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie L","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School, Norris Cotton Cancer Center , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carli R","family":"Clemis","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School, Norris Cotton Cancer Center , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University , Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A","family":"Guevara-Pati\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago , Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jo","family":"Turk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School, Norris Cotton Cancer Center , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,1,1]]},"reference":[{"key":"2025032410555944800_r1","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1126\/science.1145720","article-title":"The genomic landscapes of human breast and colorectal cancers","volume":"318","author":"Wood","year":"2007","journal-title":"Science"},{"key":"2025032410555944800_r2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/1074-7613(95)90078-0","article-title":"A unique tumor antigen produced by a single amino acid substitution","volume":"2","author":"Monach","year":"1995","journal-title":"Immunity"},{"key":"2025032410555944800_r3","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.smim.2008.09.006","article-title":"Antigens for cancer immunotherapy","volume":"20","author":"Neller","year":"2008","journal-title":"Semin. 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