FasL-dependent regulation of the magnitude of the CD8 T cell response during lethal dose influenza virus infections (VIR5P.1144)

Abstract

Abstract Our recent work has detailed a novel regulation of the IAV-specific CD8 T cell response during lethal dose or infection with high pathogenic IAV strains. During such infections, FasL+ plasmacytoid dendritic cells (pDC) within the regional lymph nodes (LN) target and eliminate the developing Fas+ effector T cell response, therein limiting immunity and driving severe disease. While our studies have shown that pDC are sufficient to drive this mechanism (i.e. transfer of wild type pDC into gld mice results in elimination of activated CD8 T cells), antibody targeted elimination of pDC in wild type mice does not completely halt CD8 T cell apoptosis. This suggested that an additional cell type might contribute to the overall loss of CD8 T cells during lethal/high path IAV infections. Herein we describe a novel cell population which shares some common markers with both pDC and B cells, but can be distinguished from both based on unique marker expression. These FasL+ cells are found at 4.5x greater numbers in the LN of lethal vs sublethal dose IAV mice and are 8.5x more prevalent than pDC with those LN. Further our results suggest that the FasL+ phenotype within this cell population segregates to BST2+ cells. Our current studies are focused on determining the factors regulating this novel cell population and it’s relative contribution to the overall FasL-dependent control of the magnitude of the CD8 T cell response during IAV infections.