CD40-independent pathways of T cell help for priming of CD8+ cytotoxic T lymphocytes

被引:172
作者
Lu, ZB [1 ]
Yuan, LX [1 ]
Zhou, XZ [1 ]
Sotomayor, E [1 ]
Levitsky, HI [1 ]
Pardoll, DM [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21231 USA
关键词
cross-priming; dendritic cells; CD40; CD4(+) help; CD8(+) cytotoxic T lymphocytes;
D O I
10.1084/jem.191.3.541
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In many cases, induction of CD8(+) CTL responses requires CD4(+) T cell help. Recently, it has been shown that a dominant pathway of CD4(+) help is via antigen presenting cell (APC) activation through engagement of CD40 by CD40 ligand on CD4(+) T cells. To further study this three cell interaction, we established an in vitro system using dendritic cells (DCs) as APCs and influenza hemagglutinin (HA) class I and II peptide-specific T cell antigen receptor transgenic T cells as cytotoxic T lymphocyte precursors and CD4(+) T helper cells, respectively. We found that CD4(+) T cells can provide potent help for DCs to activate CD8(+) T cells when antigen is provided in the form of either cell lysate, recombinant protein, or synthetic peptides. Surprisingly, this help is completely independent of CD40. Moreover, CD40-independent CD4(+) help can be documented in vivo. Finally, we show that CD40-independent T cell help is delivered through both sensitization of DCs and direct CD4(+)-CD8(+) T cell communication via lymphokines. Therefore, we conclude that CD4(+) help comprises at least three components: CD40-dependent DC sensitization, CD40-independent DC sensitization, and direct lymphokine-dependent CD4(+)-CD8(+) T cell communication.
引用
收藏
页码:541 / 550
页数:10
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