Mast cell-mediated antigen presentation regulates CD8 T cell effector functions (33.15)

Abstract

Abstract Mast cells (MCs) - long-living cells at sites of host-environment interphase, are important players of the innate immunity and central regulatory cells in adaptive immunity. We have previously described that MCs can detect viral infections and that TLR3-activated MCs contribute to antiviral host defence. MCs can regulate CD8 T cell- dependent autoimmune responses and CD8 T cell chemotaxis. Using three model antigens, we demonstrate that MCs induce antigen-specific CD8 T cell activation and proliferation. This requires direct cell contact and MHC class I-dependent antigen cross-presentation by MCs and induces the secretion of IL-2, IFN-γ and MIP-1α by CD8 T cells. Furthermore, MCs regulate antigen-specific CD8 T cell cytotoxicity by increasing granzyme B expression and promoting CD8 T cell degranulation. MCs also upregulate their expression of costimulatory molecules, and release the T cell proliferation inducer osteopontin upon direct contact. In vivo, adoptive transfer of antigen-pulsed MCs induces MHC class I-dependent, antigen-specific CD8 T cell proliferation. Furthermore, we characterised the bidirectional crosstalk between MCs and CD8 T cells and identified a new pathway of MC activation induced by MC interaction with CD8 T cells. Specifically, a number of genes coding for proteins involved in the IFN-mediated antiviral response are upregulated upon MC-CD8 T cell interaction.