Tumor-specific CD4+ T cells have a major "post-licensing" role in CTL mediated anti-tumor immunity

被引:287
作者
Marzo, AL
Kinnear, BF
Lake, RA
Frelinger, JJ
Collins, EJ
Robinson, BWS
Scott, B
机构
[1] Monash Univ, Monash Inst Reprod & Dev, Ctr Funct Gen & Human Dis, Clayton, Vic 3168, Australia
[2] Univ Western Australia, Queen Elizabeth II Med Ctr, Dept Med, Nedlands, WA 6009, Australia
[3] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
关键词
D O I
10.4049/jimmunol.165.11.6047
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A number of tumor studies have indicated a link between CD4 help and the magnitude and persistence of CTL activity; however, the mechanisms underlying this have been largely unclear. To evaluate and determine the mechanisms by which CD4(+) T cells synergize,vith CD8(+) T cells to prevent tumor growth, we used the novel technique of monitoring in vivo CTL by labeling target cells with CFSE. This approach was supported by the direct visualization of CTL using peptide-MHC tetramers to follow tumor-specific T cells. The data presented demonstrate that while cotransfer of Ag-specific CD4(+) T cells was not required for the generation of CTLs, because adoptive transfer of CD8(+) T cells alone was sufficient, CD4(+) T cells were required for the maintenance of CD8(+) T cell numbers. Our data suggest that there is a correlation among the number of CD8(+) T cells, in vivo CTL function, and IFN-gamma production, with no evidence of a partial or nonresponsive phenotype among tetramer-positive cells. We also show that CD4(+) T cells are required for CD8(+) T cell infiltration of the tumor.
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收藏
页码:6047 / 6055
页数:9
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