Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during Viral Infection Requires Crosspriming by DNGR-1+ Dendritic Cells

Abstract

Despite the crucial role of tissue-resident memory T (Trm) cells in protective immunity, their priming remains poorly understood. Here, we have shown differential priming requirements for Trm versus circulating memory CD8⁺ T cells. In vaccinia cutaneous-infected mice, DNGR-1-mediated crosspresentation was required for optimal Trm cell priming but not for their skin differentiation or for circulating memory T cell generation. DNGR-1⁺ dendritic cells (DCs) promoted T-bet transcription-factor induction and retention of CD8⁺ T cells in the lymph nodes (LNs). Inhibition of LN egress enhanced Trm cell generation, whereas genetic or antibody blockade of DNGR-1 or specific signals provided during priming by DNGR-1⁺ DCs, such as interleukin-12 (IL-12), IL-15, or CD24, impaired Trm cell priming. DNGR-1 also regulated Trm cell generation during influenza infection. Moreover, protective immunity depended on optimal Trm cell induction by DNGR-1⁺ DCs. Our results reveal specific priming requirements for CD8⁺ Trm cells during viral infection and vaccination.