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

Abstract

Summary 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.

Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria

“…6F). Of note, and agreeing with a previous study (75), the proportion of T-bet + CD8 + T cells was also markedly reduced in mice depleted of CD8 + DC. These results suggested a major role for CD8 + DC in promoting T-bet expression in CD4 and CD8 T cells, and a lower, but significant, contribution to the generation of Tfh cells.…”

“…DC subsets can influence the expression of transcription factors by T cells and drive their differentiation into particular Th phenotypes (35,36,(73)(74)(75). To address the role of CD8 + DC on the differentiation of PbT-II cells after PbA infection, XCR1-DTRvenus mice were adoptively transferred with PbT-II cells and then infected with 10 4 PbA iRBC.…”

Monocyte differentiation and antigen-presenting functions

“…Another major functional difference between the APC subtypes is that even when they induce the proliferation of the same cognate T cell, they imprint a different fate upon the resulting migratory T cells, specifically, BATF3 + DCs imprint resident memory CD8 + T cells, whereas IRF4 + DCs imprint central memory CD8 + T cells 103,109 . At this point, it is unclear what type of T cell LY6C + monocytes preferentially imprint and under what conditions.…”

Tissue-Specific Control of Tissue-Resident Memory T Cells

“…37 CD8α + DCs in mouse lymphoid organs and CD103 + DCs in non-lymphoid organs express chemokine receptor Xcr1 and C-type lectin DNGR-1 (encoded by Clec9a ). This subset of DCs develop in a transcription factor Batf3-dependent manner and exhibit superior capacity to cross-Present exogenous antigen to CD8 + T cells.…”