Journal of Leukocyte Biology | |
Direct in vivo evidence of CD4+ T cell requirement for CTL response and memory via pMHC-I targeting and CD40L signaling | |
Philip Griebel– and1  John R. Gordon1  Jim Xiang, 1  Sean J. Mulligan1  Khawaja Ashfaque Ahmed, 1  Manjunatha Ankathatti Munegowda1  Lu Wang, 1  | |
[1] Research Unit, Saskatchewan Cancer Agency, Departments of Oncology and Physiology and Division of Respirology, Critical Care and Sleep Medicine, –Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan Canada | |
关键词: dendritic cells; antigen presentation; immune response; adaptive immunity; | |
DOI : 10.1189/jlb.1211631 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
CD4+ T cell help contributes critically to DC-induced CD8+ CTL immunity. However, precisely how these three cell populations interact and how CD4+ T cell signals are delivered to CD8+ T cells in vivo have been unclear. In this study, we developed a novel, two-step approach, wherein CD4+ T cells and antigen-presenting DCs productively engaged one another in vivo in the absence of cognate CD8+ T cells, after which, we selectively depleted the previously engaged CD4+ T cells or DCs before allowing interactions of either population alone with naïve CD8+ T cells. This protocol thus allows us to clearly document the importance of CD4+ T-licensed DCs and DC-primed CD4+ T cells in CTL immunity. Here, we provide direct in vivo evidence that primed CD4+ T cells or licensed DCs can stimulate CTL response and memory, independent of DC-CD4+ T cell clusters. Our results suggest that primed CD4+ T cells with acquired pMHC-I from DCs represent crucial “immune intermediates†for rapid induction of CTL responses and for functional memory via CD40L signaling. Importantly, intravital, two-photon microscopy elegantly provide unequivocal in vivo evidence for direct CD4-CD8+ T cell interactions via pMHC-I engagement. This study corroborates the coexistence of direct and indirect mechanisms of T cell help for a CTL response in noninflammatory situations. These data suggest a new “dynamic model of three-cell interactions†for CTL immunity derived from stimulation by dissociated, licensed DCs, primed CD4+ T cells, and DC-CD4+ T cell clusters and may have significant implications for autoimmunity and vaccine design.
【 授权许可】
Unknown
【 预 览 】
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RO201912010183207ZK.pdf | 42KB | download |