Gamma delta T cells in the peripheral blood of individuals from an area of holoendemic Plasmodium falciparum transmission.

gamma delta T cells bearing V gamma 9 T cell receptors from unexposed Caucasian donors make large responses to Plasmodium falciparum in vitro. This finding, together with observations of others showing high levels of V gamma 9+ T cells in the blood of infected non-immune individuals, led us to hypothesize that the response of these cells might contribute to the pathology of P. falciparum malaria. Acquisition of immunity to disease in people naturally exposed to infection may therefore be due in part to down-regulation or alteration of the function of gamma delta T cells. Supporting this view, and in contrast to infection in non-immune individuals, V gamma 9+ T cells are not elevated in peripheral blood of children or adults living in an endemic area despite constant exposure to P. falciparum. After in vitro stimulation with P. falciparum, however, the expansion of V gamma 9+ cells from the African donors is of similar magnitude to that observed for non-exposed Europeans. Thus, although these cells are not elevated in peripheral blood, they are still able to respond to P. falciparum antigens. In adult European donors the major gamma delta T cell population in peripheral blood is V gamma 9+ (approximately 70% of all gamma delta cells), whereas in the majority of adult Africans V delta 1+ V gamma 9- T cells predominated (approximately 70% of total gamma delta cells).

Quantitative analysis of the response of human T cell receptor V gamma 9+ cells to Plasmodium falciparum.

Plasmodium falciparum stimulates peripheral blood gamma delta + T cells from unexposed donors. The responding cells bear V gamma 9+ chains of the T cell receptor, the majority of which, but not all, are associated with V delta 2 chains. We have analyzed whether the precursor frequency of these V gamma 9+ cells approaches that expected of superantigens or mitogens and whether, like a superantigen, the response is major histocompatibility complex (MHC) unrestricted. Limiting dilution analyses of the response of enriched gamma delta + T cells to P.falciparum using autologous and heterologous antigen-presenting cells suggest that the response is more characteristic of an antigen-specific MHC-restricted response. The frequencies are lower than would be expected if all V gamma 9+ cells respond, and there is a dramatically reduced response when allogeneic antigen-presenting cells are used.