B cells eliminate virus-specific CD8 T cells through a FasL:Fas dependent mechanism during high-dose influenza virus infections.

Abstract

Abstract Our prior studies have shown that after high-dose inoculums or infection with high-pathogenic strains of influenza A virus (IAV), the IAV-specific CD8 T cell response is targeted and killed by plasmacytoid dendritic cells (pDCs) within the draining lymph nodes (LN) in a FasL:Fas (pDC:T cells) dependent manner. This limits host immunity and drives severe disease. Although donor pDCs are sufficient to drive this response in FasL defective gld mice, our recent findings show that FasL+ B cells out number FasL+ pDCs 50:1 within the LN during high-dose IAV infections. This suggested that B cells might contribute to the overall loss of CD8 T cells during high-dose/high-pathogenic IAV infections. Further, we have identified at least two subsets of FasL+ B cells (i.e. CD11c+ and CD11c−) that accumulate at higher numbers within the LN following high- vs. low-dose IAV infections. Additionally, our results suggest that FasL expression by CD11c+ and CD11c− B cells is induced in part by IL-12p40, which is expressed at higher levels in the LN during high-dose IAV infections. Finally, adoptive transfer studies utilizing gld host mice demonstrate that both donor CD11c+ and CD11c− B cell subsets can eliminate IAV-specific CD8 T cells in a FasL:Fas dependent manner during high-dose IAV infections. Therefore overall it appears that FasL+ B cells contribute to the loss of IAV-specific CD8 T cells during high-dose IAV infections ultimately leading to the death of the host.