Immunotherapy with live BCG plus heat killed Leishmania induces a T helper1-like response in American cutaneous leishmaniasis patients

Previous work has shown that American cutaneous leishmaniasis (ACL) patient s treated with viable BCG plus heat killed promastigotes of Leishmania amaz onensis show the same rate of cure as patients receiving conventional chemo therapy. The treatment is safe and economical, but the immunological correl ates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled be fore and after therapy, and in 10 endemic controls. Lymphocyte proliferatio n, interferon (IFN)-gamma and interleukin (IL)-5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimul ation, and serum IL-5 levels, were analysed. In endemic volunteers, prolife rative responses to BCG were high and IFN-gamma responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low prol iferative and high IFN-gamma responses to BCG. Treatment enhanced the IFN-g amma response and further decreased the proliferative response to BCG, espe cially in MCL patients. LCL and MCL patients showed an increase in prolifer ative and IFN-gamma responses to MEL with treatment, but the response was n ot exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL-5 production was low in T cell assays, and > 62% of unt reated patients had very low serum IL-5 levels. There were no significant c hanges in serum IL-5 with treatment. Overall results show enhanced antigen- specific IFN-gamma responses to the two components of the immunotherapy, li ve M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clini cal cure mediated by IFN-gamma.