Defective MHC Class II Presentation by Dendritic Cells Limits CD4 T Cell Help for Antitumor CD8 T Cell Responses1
Defective MHC Class II Presentation by Dendritic Cells Limits CD4 T Cell Help for Antitumor CD8 T Cell Responses1
复制标题
树突状细胞的 MHC II 类缺陷表达限制了 CD4 T 细胞对抗肿瘤 CD8 T 细胞反应的帮助1
作者：
Michael Y. Gerner;K. Casey;M. Mescher
Cancer immunosurveillance failure is largely attributed to insufficient activation signals and dominant inhibitory stimuli for tumor Ag (TAg)-specific CD8 T cells. CD4 T cells have been shown to license dendritic cells (DC), thereby having the potential for converting CD8 T cell responses from tolerance to activation. To understand the potential cooperation of TAg-specific CD4 and CD8 T cells, we have characterized the responses of naive TCR transgenic CD8 and CD4 T cells to poorly immunogenic murine tumors. We found that whereas CD8 T cells sensed TAg and were tolerized, the CD4 T cells remained ignorant throughout tumor growth and did not provide help. This disparity in responses was due to normal TAg MHC class I cross-presentation by immature CD8α+ DC in the draining lymph node, but poor MHC class II presentation on all DC subsets due to selective inhibition by the tumor microenvironment. Thus, these results reveal a novel mechanism of cancer immunosubversion, in which inhibition of MHC-II TAg presentation on DC prevents CD4 T cell priming, thereby blocking any potential for licensing CD8α+ DC and helping tolerized CD8 T cells.
影响因子：
32.4
作者：
Badovinac, Vladimir P.;Haring, Jodie S.;Harty, John T.
通讯作者：
Harty, John T.
影响因子：
32.4
作者：
Shrikant, P;Khoruts, A;Mescher, MF
通讯作者：
Mescher, MF