Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can regulate dendritic cell-induced activation and cytotoxicity CD8+ T cells independently of CD4+ T cell help

被引:61
作者
McCoy, KD [1 ]
Hermans, IF [1 ]
Fraser, JH [1 ]
Le Gros, G [1 ]
Ronchese, F [1 ]
机构
[1] Wellington Sch Med, Malaghan Inst Med Res, Wellington S, New Zealand
基金
英国惠康基金;
关键词
CTLA-4 (CD152); CD8(+)T cells; dendritic cells; CD4(+) T cells; cytotoxicity;
D O I
10.1084/jem.189.7.1157
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The mechanisms that regulate the strength and duration of CD8(+) cytotoxic T cell activity determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8(+) T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on purified CD8(+) T cells caused decreased proliferative responses to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of CTLA-4 by neutralizing anti-CTLA-4 mAb greatly enhanced the accumulation, activation, and cytotoxic activity of CD8(+) T cells induced by immunization with Ag on dendritic cells (DC). This enhanced response did not require the expression of MHC class II molecules on DC or the presence of CD4(+) T cells. These results demonstrate that CTLA-4 blockade is able to directly enhance the proliferation and activation of specific CD8(+) T cells, indicating its potential for tumor immunotherapy even ill situations in which CD4(+) T cell help is limited or absent.
引用
收藏
页码:1157 / 1162
页数:6
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