TY - JOUR
T1 - Defective MHC class II presentation by dendritic cells limits CD4 T cell help for antitumor CD8 T cell responses
AU - Gerner, Michael Y.
AU - Casey, Kerry A.
AU - Mescher, Matthew F.
PY - 2008
Y1 - 2008
N2 - Cancer immunosurveillancc failure is largely attributed to insufficient activation signals and dominant inhibitory stimuli for tumor Ag (TAg)-speciflc 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.
AB - Cancer immunosurveillancc failure is largely attributed to insufficient activation signals and dominant inhibitory stimuli for tumor Ag (TAg)-speciflc 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.
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U2 - 10.4049/jimmunol.181.1.155
DO - 10.4049/jimmunol.181.1.155
M3 - Article
C2 - 18566380
AN - SCOPUS:47949091237
VL - 181
SP - 155
EP - 164
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -