Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions

Abstract

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.

Diminished Innate Antiviral Response to Adenovirus Vectors in cGAS/STING-Deficient Mice Minimally Impacts Adaptive Immunity

“…In vivo, DC maturation and migration following virus activation are complex and dynamic processes leading to CD4 and CD8 T-cell priming. Recent reports have revealed that for different viruses, infection and DC migration to lymph nodes result in distinct spatially and temporally defined interactions between CD4 and CD8 T cells and multiple subsets of DCs (67,68). The factors that influence these distinct DC interactions with T-cell subsets have not been fully established for Ad infections.…”

CD27 Agonism Plus PD-1 Blockade Recapitulates CD4+ T-cell Help in Therapeutic Anticancer Vaccination

“…We here make use of However, they next contacted the same XCR1 þ DCs. This second priming event promoted memory precursor formation and recall capacity of CD8 þ T cells and thus proved to be the platform for delivery of CD4 þ T-cell help (31).…”

Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node

“…During the revision of this paper, the spatiotemporal characterization of antigen-specific CD4 + T cells and CD8 + T cells in the SDLNs was reported in HSV-1 or vaccinia virus infection (25,26). Although the location and/or timing of initial activation of CD4…”

“…It will be needed to investigate whether Xcr1-expressing LN-resident DCs sample antigen from the subcapsular sinus and migrate to the T-cell zone for interacting with CD8 + T cells. More importantly, future studies should perform similar imaging analyses with the Xcr1 KikGR/+ mouse strain during different types of immune responses, because capabilities of the migratory and resident DC subsets to interact with CD8 + T cells are likely to be affected by the types of vaccines and microbes (17,25,26,28).…”