Tay Neil Q, Lee Debbie C P, Chua Yen Leong, Prabhu Nayana, Gascoigne Nicholas R J, Kemeny David M
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Immunol. 2017 Nov 6;8:1484. doi: 10.3389/fimmu.2017.01484. eCollection 2017.
CD8 T cells play an important role in providing protective immunity against a wide range of pathogens, and a number of different factors control their activation. Although CD40L-mediated CD40 licensing of dendritic cells (DCs) by CD4 T cells is known to be necessary for the generation of a robust CD8 T cell response, the contribution of CD8 T cell-expressed CD40L on DC licensing is less clear. We have previously shown that CD8 T cells are able to induce the production of IL-12 p70 by DCs in a CD40L-dependent manner, providing some evidence that CD8 T cell-mediated activation of DCs is possible. To better understand the role of CD40L on CD8 T cell responses, we generated and characterized CD40L-expressing CD8 T cells both and . We found that CD40L was expressed on 30-50% of effector CD8 T cells when stimulated and that this expression was transient. The expression of CD40L on CD8 T cells promoted the proliferation and differentiation of both the CD40L-expressing CD8 T cells and the bystander effector CD8 T cells. This process occurred a cell-extrinsic manner and was mediated by DCs. These data demonstrate the existence of a mechanism where CD8 T cells and DCs cooperate to maximize CD8 T cell responses.
CD8 T细胞在提供针对多种病原体的保护性免疫方面发挥着重要作用,并且多种不同因素控制着它们的激活。虽然已知CD4 T细胞通过CD40L介导的树突状细胞(DC)的CD40许可对于产生强大的CD8 T细胞反应是必要的,但CD8 T细胞表达的CD40L对DC许可的贡献尚不清楚。我们之前已经表明,CD8 T细胞能够以CD40L依赖的方式诱导DC产生IL-12 p70,这提供了一些证据表明CD8 T细胞介导的DC激活是可能的。为了更好地理解CD40L在CD8 T细胞反应中的作用,我们生成并表征了在 和 中表达CD40L的CD8 T细胞。我们发现,当受到刺激时,30% - 50%的效应CD8 T细胞表达CD40L,并且这种表达是短暂的。CD8 T细胞上CD40L的表达促进了表达CD40L的CD8 T细胞和旁观者效应CD8 T细胞的增殖和分化。这个过程以细胞外方式发生并且由DC介导。这些数据证明了一种机制的存在,即CD8 T细胞和DC合作以最大化CD8 T细胞反应。