cDC1 licensing is essential for the survival but not priming of CD8+ T cell responses during vaccination 4659

Abstract Description Type I conventional dendritic cells (cDC1) have been shown to serve a multifacted role in the induction of CD8+ T cell responses from initial antigen processing and presentation to serving as a licensed platform for CD4+ T cell help. cDC1 have been previously shown to be critical for the generation of a protective, antigen-specific CD8+ T cell response after a single low dose immunization with an attenuated strain of Toxoplasma gondii. Surprisingly, this CD8+ T cell defect was not a result of an inability to prime CD8+ T cells as infected macrophages can present parasite antigen to CD8+ T cells via MHC class I. Instead, the absence of cDC1 results in parasite-specific CD8+ T cells that are defective in upregulating nutrient and cytokine receptors and exhibit increased rates of cell death in early divisions after priming. Lineage-specific deletion of β2-microglobulin from cDC1s showed that CD8+ T cells require MHC-I interactions with cDC1, implicating a role for cDC1 licensing in mediating T cell help during vaccination. Immunization of CD40-/- mice showed a significant decrease in the number of antigen-specific CD8+ T cells and a failure of these cells to differentiate into effector T cells. Further, lineage-specific deletion of CD40 in cDC1 resulted in a defective CD8+ T cell response similar to that in CD40-/- mice. Ongoing work is focusing on understanding the impact of the loss of CD40-mediated T cell help on the early expansion of the CD8+ T cell response after priming. Funding Sources Supported by NIH AI-160664; NIH AI-163671. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)