Perturbation and proinflammatory type activation of V delta 1(+) gamma delta T cells in African children with Plasmodium falciparum malaria

gamma delta T cells have variously been implicated in the protection agains t, and the pathogenesis of, malaria, but few studies have examined the gamm a delta T-cell response to malaria in African children, who suffer the larg e majority of malaria associated morbidity and mortality. This is unfortuna te, since available data suggest that simple extrapolation of conclusions d rawn from studies of nonimmune adults ex vivo and in vitro is not always po ssible. Here we show that both the frequencies and the absolute numbers of gamma delta T cells are transiently increased following treatment of Plasmo dium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. T he bulk of the gamma delta T cells involved in this perturbation expressed V delta1 and had a highly activated phenotype. Analysis of the T-cell recep tors (TCR) of the V delta1(+) cell population at the peak of their increase showed that all expressed V gamma chains were used, and CDR3 length polymo rphism indicated that the expanded V delta1 population was highly polyclona l. A very high proportion of the V delta1(+) T cells produced gamma interfe ron, while fewer V delta1(+) cells than the average proportion of all CD3() cells produced tumor necrosis factor alpha. No interleukin 10 production was detected among TCR-gamma delta (+) cells in general or V delta1(+) cell s in particular. Taken together, our data point to an immunoregulatory role of the expanded V delta1(+) T-cell population in this group of semi-immune P, falciparum malaria patients.