Distinct APC subtypes drive spatially segregated CD4+ and CD8+ T-cell effector activity during skin infection with HSV-1

Efficient infection control requires potent t-cell responses at sites of pathogen replication. however,the regulation of t-cell effector function in situ remains poorly understood. here,we show key differences in the regulation of effector activity between cd4+ and cd8+ t-cells during skin infection with hsv-1. ifn-g-producing cd4+ t cells disseminated widely throughout the skin and draining lymph nodes (ln),clearly exceeding the epithelial distribution of infectious virus. by contrast,ifn-g-producing cd8+ t cells were only found within the infected epidermal layer of the skin and associated hair follicles. mechanistically,while various subsets of lymphoid- and skin-derived dendritic cells (dc) elicited ifn-g production by cd4+ t cells,cd8+ t cells responded exclusively to infected epidermal cells directly presenting viral antigen. notably,uninfected cross-presenting dcs from both skin and lns failed to trigger ifn-g production by cd8+ t-cells. thus,we describe a previously unappreciated complexity in the regulation of cd4+ and cd8+ t-cell effector activity that is subsetspecific,microanatomically distinct and involves largely non-overlapping types of antigen-presenting cells (apc). ©2014 macleod et al.