期刊
JOURNAL OF IMMUNOLOGY
卷 186, 期 1, 页码 275-283出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001308
关键词
-
类别
资金
- National Institutes of Health [R01 CA120777, P20 RR 16437 COBRE, R21CA127037-01A1]
- Melanoma Research Foundation
- American Cancer Society-Illinois Division [07-20]
- American Cancer Society [ACSLIB112496-RSG]
- Cancer Research Foundation
- Dartmouth Medical School
- NATIONAL CANCER INSTITUTE [R01CA120777, R21CA127037, P30CA023108] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR016437] Funding Source: NIH RePORTER
Treatment of tumor-bearing mice with a stimulatory Ab to glucocorticoid-induced TNFR family-related receptor (GITR) has previously been shown to elicit protective T cell responses against poorly immunogenic tumors. 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 (T-reg) 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 T-reg 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 T-reg 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. The Journal of Immunology, 2011, 186: 275-283.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据