Preferential activation and expansion of human peripheral blood γδ T cells in response to Toxoplasma gondii in vitro and their cytokine production and cytotoxic activity against T. gondii-infected cells

Studies were conducted to determine if γδ T cells participate in the immune response to Toxoplasma gondii. Preferential expansion of human γδ T cells occurred when peripheral blood T cells from either T. gondii-seronegative or seropositive individuals were incubated with autologous PBMC infected with the parasite. That γδ T cells proliferated after incubation with infected cells was confirmed using purified of γδ T cells. These T. gondii-induced γδ T cell responses did not require prior exposure to the parasite since T cells obtained from umbilical cord blood from seronegative newhorns also exhibited preferential expansion of γδ T cells. Cytofluorometric analysis of T cells obtained from either umbilical cord blood or peripheral blood from adults revealed that Vγ9⁺ and Vδ2⁺ γδ T cells responded to stimulation with infected cells. Preferential expansion of γδ T cells was not restricted by polymorphic determinants of MHC molecules. PBMC that had internalized killed parasites but not PBMC incubated with T. gondii lysate antigens also stimulated preferential expansion and activation of γδ T cells as assessed by expression of CD25 and HLA-DR molecules. Vγ9⁺Vδ2⁺ γδ T cells were cytotoxic for T. gondii-infected cells in an MHC-unrestricted manner, and produced IFN-γ, IL-2, TNF-α, but not IL-4 when incubated with cells infected with the parasite. These results suggest that rapid induction of a remarkable primary γδ T cell response may be important in the early protective immune response to T. gondii.