The Inftuence of Antigen-Presenting Cell Type and Interferon-yon Priming and Cytokine Secretion of Leishmania major-Specific T Cells

A Leishmania major-specific primary in vitro system that mimics the immune response of infected mice was used to determine the role that dendritic cells, B cells, and macrophages play in L. major T cell priming. Their relative priming potential (in order) was dendritic cells, B cells, and macrophages. Initiating primary in vitro responses with cell populations depleted of either B or dendritic cells modestly enhanced interferon (lFN)-1 ' production; deleting both cells markedly en-hanced IFN-1 ' production. Thus, macrophages were the most effective cell for eliciting L. major Thl cells. The effects of exogenously added IFN-1 ' or neutralizing anti-IFN-1 ' were also studied. With cells from genetically susceptible BALB/c mice, IFN-1 ' inhibited proliferation and interleukin-4 secretion by T cells, whereas with resistant C57BL/6 cells, IFN-1 ' enhanced IFN-1 ' secretion. These results could not be explained by differences in IFN-1 ' receptor expression. Since their description by Mosmann and Coffman [I], the Thl and Th2 subsets of the CD4 T cell compartment have been shown to playa critical role in many chronic diseases. A well-studied example is experimental murine cutaneous leish-maniasis in which selective activation ofThl cells is associate