Programmed death ligand-1 signaling within dendritic cells facilitates resident memory T cell responses during cutaneous vaccinia infection 3288

Abstract Description Dendritic cell (DC) migration during viral challenge is a critical function required for initiating T-cell responses. Antigen-bearing DCs migrate to the draining lymph node (dLN) and present antigens bound by MHC to T-cells. A critical DC interaction is ligation of programmed death ligand-1 (PDL1) with CD80 as these interactions facilitate intracellular signaling through the cytoplasmic domain of PDL1 needed for DC migration and resultant T-cell responses. Here, we show that migratory cDC1s accumulate in the skin of PDL1 cytoplasmic mutant (CyMt) mice after vaccinia (VacV) infection rather than localize to the dLN as seen in wildtype mice. This impaired cDC1 migration within PDL1 CyMt mice resulted in enhanced formation of antigen-specific CD8+ memory T cells after resolution of VacV infection. This was not due to differences in cross-presentation ability of cDC1s between wildtype and PDL1 CyMt mice, but due to retention of the migratory cDC1s in the skin. We also found that antigen-specific CD8+ T cells within the skin and dLN displayed a tissue resident memory phenotype with higher surface expression of CD69 and CD103. However, upon reinfection in PDL1 CyMt mice, these memory T cells increased expression of exhaustion markers (PD-1 and Lag3) and had decreased secretion of IFNg and IL-2. These findings establish how PDL1 DC intrinsic signals facilitate proper migration and programming of resident memory T cells that are necessary to respond to tissue-specific reinfection. Funding Sources R01 AI121209 R01 AI155474 F30 AI176607 Topic Categories Viral Immunology (VIR)