Human gamma delta T cell subset-proliferative response to malarial antigen in vitro depends on CD4+ T cells or cytokines that signal through components of the IL-2R.

We examined the cellular and molecular basis of the proliferative response of human gamma delta T cells in cultures of PBMC stimulated with blood-stage Plasmodium falciparum malarial Ag. Flow cytometry revealed that maximal gamma delta T cell proliferation occurs after maximal CD4+ alpha beta T cell proliferation. Depletion of CD4+ T cells from PBMC before stimulation with malarial Ag markedly reduces the number of proliferating gamma delta T cells, which suggests that CD4+ T cells function in providing help to gamma delta T cells to respond to this parasite Ag. Removal of gamma delta T cells, however, did not alter the expansion of the CD4+ T cell subset. The addition of exogenous IL-2, IL-4, or IL-15 restored the capacity of gamma delta T cells to proliferate in Ag-stimulated cultures of PBMC depleted of CD4+ T cells. mAbs specific for the alpha- and beta-subunits of the IL-2 receptor inhibit the gamma delta T cell subset expansion in cultures stimulated with malarial Ag. Taken together, these findings suggest that the proliferation of gamma delta T cells in response to malarial Ag is dependent on the presence of CD4+ alpha beta T cells, but the requirement for CD4+ alpha beta T cells can be met by cytokines that use the IL-2R.