Summary Host defense against viruses and intracellular parasites depends on effector CD8+ T cells whose optimal clonal expansion, differentiation, and memory properties require signals from CD4+ T cells. Here we addressed the role of dendritic cell (DC) subsets in initial activation of the two T cell types and their co-operation. Surprisingly, initial priming of CD4+ and CD8+ T cells was spatially segregated within the lymph node and occurred on different DC with temporally distinct patterns of antigen-presentation via MHCI vs. MHCII molecules. DC that co-present antigen via both MHC molecules were detected at a later stage; these XCR1+-DC are the critical platform involved in CD4+ T cell augmentation of CD8+ T cell responses. These findings delineate the complex choreography of cellular interactions underlying effective cell-mediated anti-viral responses, with implications for basic DC subset biology as well as for translational application to the development of vaccines that evoke optimal T cell immunity.

Summary Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DC). Plasmacytoid DC (pDC) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where and how they exert their functions. We found that pDC accumulated at sites of CD8+ T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8+ T cells orchestrated the local recruitment of lymph node resident XCR1 chemokine receptor-expressing DC via secretion of the XCL1 chemokine. Functionally, this CD8+ T cell mediated reorganization of the local DC network allowed for the interaction and cooperation of pDC and XCR1+ DC, thereby optimizing XCR1+ DC maturation and cross-presentation. These data support a model in which CD8+ T cells upon activation create their own optimal priming microenvironment by recruiting additional DC subsets to the site of initial antigen recognition.

21 ] i may in turn activate TRPA 1 leading to a greater rise in [Ca 21 ] i . We also recognize that these studies were performed in vitro, which may not fully recapitulate what occurs in vivo. Finally, studies using primary bronchial epithelial cells from deceased donors are intrinsically limited by the availability of donor cells, especially in the pediatric age group. Additionally, history of atopic status and lung function is frequently not available, as well as comorbidities and cause of death. Thus, it is possible that the age effect could be explained by other factors and future studies will need to be done using cells from identified samples from patients with documented asthma status and severity.In conclusion, the results of this study show for the first time that lower airway epithelium from asthmatic children displays elevated basal TRPV 1 activity when compared with that of nonasthmatic controls. We have also shown that RSV infection of epithelial cells from asthmatic children-but not from adults-leads to an increase in overall TRPV 1 activation. Pharmacological inhibition of TRPV 1 may lead in the future to strategies that might reduce the impact of RSV infections in both asthmatic and nonasthmatic children.