Plasmacytoid dendritic cells control influenza-specific CD8 T cells numbers through regulated FasL expression during lethal influenza virus infections (44.3)

Abstract

Abstract Previously we have demonstrated that the difference in survival of high versus low dose conventional influenza infections is linked to a severe T cell lymphopenia in high dose infections similar to what has been described in lethal H5N1 infections. This difference in T cell numbers is mediated by a novel regulatory mechanism where lymph node dendritic cells (LNDC) eliminate influenza-specific CD8 T cells in a FasL/Fas dependent manner within the LN in high but not low dose infections. Currently, it is unknown which LNDC subsets and what additional factors are required for driving this CD8 T cell apoptosis. Our results demonstrate that high dose pDC directly induce apoptosis of influenza-specific CD8 T cells ex vivo. This elimination occurs in the absence of influenza antigen presentation as peptide pulsing of pDC abrogates the induction of apoptosis. Further pDC downmodulate FasL expression, a process that appears to be dependent upon rDC migration and reduced rDC production of IL-12 p40 homodimer during low dose infections, therein allowing influenza-specific CD8 T cells to escape pDC induced apoptosis. Our results detail a heretofore undescribed role for pDC during influenza virus infections whereby pDC control the overall magnitude of the influenza-specific CD8 T cell response within the LN and ultimately, therein contribute to the outcome of influenza virus infections.