Role of CD4 T cell help and costimulation in CD8 T cell responses during listeria monocytogenes infection

被引:135
作者
Shedlock, DJ
Whitmire, JK
Tan, J
MacDonald, AS
Ahmed, R
Shen, H
机构
[1] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Pathobiol, Philadelphia, PA 19104 USA
[3] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[4] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA
关键词
D O I
10.4049/jimmunol.170.4.2053
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD4 T cells are known to assist the CD8 T cell response by activating APC via CD40-CD40 ligand (L) interactions. However, recent data have shown that bacteria] products can directly activate APC through Toll-like receptors, resulting in up-regulation of costimulatory molecules necessary for the efficient priming of naive T cells. It remains unclear what role CD4 T cell help and various costimulation pathways play in the development of CD8 T cell responses during bacterial infection. In this study, we examined these questions using an intracellular bacterium, Listeria monocytogenes, as a model of infection. In CD4 T cell-depleted, CD4(-/-), and MHC class II-/- mice, L. monocytogenes infection induced CD8 T cell activation and primed epitope-specific CD8 T cells to levels commensurate with those in normal C57BL/6 mice. Furthermore, these epitope-specific CD8 T cells established long-term memory in CD4(-/-) mice that was capable of mounting a protective recall response. In vitro analysis showed that L monocytogenes directly stimulated the activation and maturation of murine dendritic cells. The CD8 T cell response to L. monocytogenes was normal in CD40L(-/-) mice but defective in CD28(-/-) and CD137L(-/-) mice. These data show that in situations where infectious agents or immunogens can directly activate APC, CD8 T cell responses are less dependent on CD4 T cell help via the CD40-CD40L pathway but involve costimulation through CD137-CD137L and B7-CD28 interactions.
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页码:2053 / 2063
页数:11
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