Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients

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Abstract
Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)‐γ and interleukin (IL)‐5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL‐5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN‐γ responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN‐γ responses to BCG. Treatment enhanced the IFN‐γ response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN‐γ responses to MEL with treatment, but the response was not 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 untreated patients had very low serum IL‐5 levels. There were no significant changes in serum IL‐5 with treatment. Overall results show enhanced antigen‐specific IFN‐γ responses to the two components of the immunotherapy, live 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 clinical cure mediated by IFN‐γ.