SWITCH FROM A TYPE-2 TO A TYPE-1 T-HELPER CELL RESPONSE AND CURE OF ESTABLISHED LEISHMANIA-MAJOR INFECTION IN MICE IS INDUCED BY COMBINED THERAPY WITH INTERLEUKIN-12 AND PENTOSTAM

Successful treatment in allergic, autoimmune, and infectious diseases often requires altering the nature of a detrimental immune response mediated by a particular CD4(+) T helper (T-h) cell subset. While several factors contribute to the development of CD4(+) T-h1 and T-h2 cells, the requirements for switching an established response are not understood. Here we use infection with Leishmania major as a model to investigate those requirements. We report that treatment with interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal drug Pentostam, induces healing in L. major-infected mice and that healing is associated with a switch from a T-h2 to a T-h1 response. The data suggest that decreasing antigen levels may be required for IL-12 to inhibit a T-h2 response and enhance a T-h1 response. These observations are important for treatment of nonhealing forms of human leishmaniasis and also demonstrate that in a chronic infectious disease an inappropriate T-h2 response can be switched to an effective T-h1 response.