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Background  An effective adaptive immune response requires activation of specific CD4 T cells. The capacity of B cells to activate CD4 T cells in human cutaneous leishmaniasis caused by  Leishmania (Viannia)  has not been evaluated.    Methods  CD4 T cell activation by B cells of cutaneous leishmaniasis patients was evaluated by culture of PBMCs or purified B cells and CD4 T cells with  Leishmania panamensis  antigens. CD4 T cell and B cell activation markers were evaluated by flow cytometry and 13 cytokines were measured in supernatants with a bead-based capture assay. The effect of  Leishmania  antigens on BCR-mediated endocytosis of ovalbumin was evaluated in the Ramos human B cell line by targeting the antigen with anti-IgM-biotin and anti-biotin-ovalbumin-FITC.    Results  Culture of PBMCs from cutaneous leishmaniasis patients with  Leishmania  antigens resulted in upregulation of the activation markers CD25 and CD69 as well as increased frequency of CD25 hi CD127 -  cells among CD4 T cells. Concomitantly, B cells upregulated the costimulatory molecule CD86. These changes were not observed in PBMCs from healthy subjects, indicating participation of  Leishmania -specific lymphocytes expanded  in vivo . Purified B cells from these patients, when interacting with purified CD4 T cells and  Leishmania  antigens, were capable of inducing significant increases in CD25 and CD69 expression and CD25 hi CD127 -  frequency in CD4 T cells. These changes were associated with upregulation of CD86 in B cells. Comparison of changes in CD4 T cell activation parameters between PBMC and B cell/CD4 T cell cultures showed no statistically significant differences; further, significant secretion of IFN-γ, TNF-α, IL-6 and IL-13 was induced in both types of cultures. Additionally, culture with  Leishmania  antigens enhanced BCR-mediated endocytosis of ovalbumin in Ramos human B cells.    Conclusions  The capacity of B cells specific for  Leishmania  antigens in peripheral blood of cutaneous leishmaniasis patients to activate CD4 T cells and induce cytokine secretion is similar to that of all cell populations present in PBMCs. This capacity implicates B cells as a plausible target for modulation of the immune response to  Leishmania  infection as a therapeutic strategy.

CD4 T cell activation by B cells in human Leishmania (Viannia)infection