IFNγ drives human primary skin mast cells to function as antigen presenting cells. (INC6P.341)

We assessed the antigen presenting ability of mature primary human skin mast cells (MCs) in vitro. MCs do not express HLA II at baseline, but do so when stimulated with IFNγ. IFNγ-primed, but not un-primed, MCs facilitated activation of Jurkat T cells by superantigen. Unlike polyclonal primary CD4+ T cells, which harbor a subset of IFNγ producing cells, Jurkat cells do not spontaneously produce IFNγ. Co-culture of un-primed MCs with CD4+ T cells for 2 days upregulated HLA II expression on MCs and subsequent superantigen mediated T cell activation. MC HLA II upregulation is primarily due to the Th1 cell subset and is prevented by IFNγ neutralizing and/or receptor blocking antibody. Superantigen bypasses HLA II-loaded peptide:T cell receptor interactions; therefore, we assessed the ability of MCs to present cytomegalovirus antigen. MCs primed ±cytomegalovirus antigen exposure for 3 days then ±IFNγ for the last 2 of those days were washed thoroughly and co-cultured with HLA-matched CD4+ cells. After one week, CD4+ T cells from cytomegalovirus seropositive, but not seronegative, individuals showed proliferation (CFSE dilution), activation (CD25high and CD69high expression), and appropriate intracellular cytokine production (IFNγ and IL-4, but not IL-17). Thus, MCs can take up, process, and present antigen in an HLA II-restricted manner, causing antigen specific activation and proliferation of CD4+ T cells.