IL-10 from T cells, but not macrophages is required for chronic disease in Leishmania mexicana infection (P3328)

Abstract

Abstract Chronic cutaneous disease of mice caused by the protozoan parasite Leishmania mexicana requires IL-10 and FcγRIII (an activating IgG receptor). Macrophages are abundant in lesions and readily secrete IL-10 in response to IgG-coated amastigote stage parasites, making macrophages a prime candidate as the critical source of IL-10. However, both direct and indirect evidence demonstrated that macrophage IL-10 is not essential for chronic disease. Specifically, macrophage-granulocyte specific IL-10-deficient mice have chronic disease identical to wild-type mice. We now show that T cell-derived IL-10 is required for chronic disease. CD4-cre IL-10flox/flox mice lack IL-10 from T cells (both CD4+ and CD8+) and heal their L. mexicana lesions. We had previously shown that depletion of CD25+ T cells had no effect on chronic disease, and thus T cells other than Treg cells should be the important source of IL-10. Given that conventional T cells do not express FcγRs, there is likely to be an indirect pathway by which FcγRIII engagement on some other cell induces IL-10 from T cells. Further work is needed to delineate these pathways.