HUMAN GAMMA-DELTA T-CELL SUBSET-PROLIFERATIVE RESPONSE TO MALARIAL ANTIGEN IN-VITRO DEPENDS ON CD4-CELLS OR CYTOKINES THAT SIGNAL THROUGH COMPONENTS OF THE IL-2R( T)

We examined the cellular and molecular basis of the proliferative resp onse 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 CD 4(+) 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 cel ls function in providing help to gamma delta T cells to respond to thi s parasite Ag. Removal of gamma delta T cells, however, did not alter the expansion of the CD4(+) T cell subset. The addition of exogenous I L-2, IL-4, or IL-15 restored the capacity of gamma delta T cells to pr oliferation Ag-stimulated cultures of PBMC depleted of CD4(+) T cells. mAbs specific for the alpha- and beta-subunits of the IL-2 receptor i nhibit the gamma delta T cell subset expansion in cultures stimulated with malarial Ag. Taken together, these findings suggest that the prol iferation of gamma delta T cells in response to malarial Ag is depende nt on the presence of CD4(+) alpha beta T cells, but the requirement f or CD4(+) alpha beta T cells can be met by cytokines that use the IL-2 R.