Control of Leishmania infantum Infection Is Associated with CD8 + and Gamma Interferon- and Interleukin-5-Producing CD4 + Antigen-Specific T Cells

Abstract

ABSTRACT Visceral leishmaniasis is a severe and lethal disease caused by the protozoan parasites of the genus Leishmania . In areas where leishmaniasis is endemic, most infected individuals control the infection and remain asymptomatic; chemotherapy of visceral leishmaniasis restores some immunity which protects against relapses. In the present study, Leishmania -specific T-cell clones were established from six asymptomatic and five cured patients. Cytokines production by these clones was analyzed. A large fraction of the parasite-specific T-cell clones from asymptomatic patients were CD8 + and produced high amounts of gamma interferon (IFN-γ). Most CD4 + T-cell clones from two asymptomatic subjects exhibited an unusual phenotype: production of high levels of IFN-γ low levels of interleukin-4, (IL-4), but high levels of IL-5. In contrast, only few parasite-specific CD8 + T-cell clones were obtained from cured patients after chemotherapy; moreover, CD4 + T-cell clones from these patients exhibited an heterogeneous profile of cytokines from Th1-like to Th2-like phenotypes. These results point to CD8 + T cells and to IL-5- and IFN-γ-producing CD4 + T cells as possible contributors to human resistance to Leishmania infection. They should stimulate new immunological approaches in the control of this disease.