Perturbation and Proinflammatory Type Activation of Vδ1 + γδ T Cells in African Children with Plasmodium falciparum Malaria

Abstract

ABSTRACT γδ T cells have variously been implicated in the protection against, and the pathogenesis of, malaria, but few studies have examined the γδ T-cell response to malaria in African children, who suffer the large majority of malaria-associated morbidity and mortality. This is unfortunate, since available data suggest that simple extrapolation of conclusions drawn from studies of nonimmune adults ex vivo and in vitro is not always possible. Here we show that both the frequencies and the absolute numbers of γδ T cells are transiently increased following treatment of Plasmodium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the γδ T cells involved in this perturbation expressed Vδ1 and had a highly activated phenotype. Analysis of the T-cell receptors (TCR) of the Vδ1 + cell population at the peak of their increase showed that all expressed Vγ chains were used, and CDR3 length polymorphism indicated that the expanded Vδ1 population was highly polyclonal. A very high proportion of the Vδ1 + T cells produced gamma interferon, while fewer Vδ1 + cells than the average proportion of all CD3 + cells produced tumor necrosis factor alpha. No interleukin 10 production was detected among TCR-γδ + cells in general or Vδ1 + cells in particular. Taken together, our data point to an immunoregulatory role of the expanded Vδ1 + T-cell population in this group of semi-immune P. falciparum malaria patients.