Leishmania major induces differential expression of costimulatory molecules on mouse epidermal cells

Levels of expression of costimulatory molecules have been proposed to influence the outcome of antigen‐specific T cell priming. We found that Leishmania major selectively modulated the expression of costimulatory molecules on various populations of epidermal cells. B7.2 expression was down‐regulated on Thy1.2+ epidermal cells (keratinocytes) from disease‐resistant C3H mice, but not from disease‐susceptible BALB/c mice. In addition, epidermal cells from BALB/c mice showed a down‐regulation of B7.1 expression on NLDC 145+ Langerhans cells. In vitroT cell priming experiments, using syngeneic epidermal cells as antigen‐presenting cells (APC), showed that the production of IFN‐γ was inhibited when either B7.1 or B7.2 signaling pathways wereblocked. Blockade of B7.2, but not B7.1, significantly inhibited the ability of epidermal cells to induce IL‐4 production from CD4+ T cells. In addition, C3H CD4+ T cells, which were unable to secrete detectable levels of IL‐4 in cultures with syngeneic APC, were now able to secrete IL‐4 following presentation of L. major antigens by congenic BALB/K epidermal cells. Conversely, C3H epidermal cells supported the priming of BALB/K CD4+ T cells for IL‐4 production in vitro. Thus, the differential expression of B7 molecules on epidermal cells may notrepresent the sole factor governing the polarization of L. major‐specific CD4+ T cells in vitro.