Abstract

Although clinical immunity to malaria eventually develops among children living in endemic settings, the underlying immunologic mechanisms are not known. The Vd2(+) subset of ?d T cells have intrinsic reactivity to malaria antigens, can mediate killing of Plasmodium falciparum merozoites, and expand markedly in vivo after malaria infection in previously naïve hosts, but their role in mediating immunity in children repeatedly exposed to malaria is unclear. We evaluated ?d T cell responses to malaria among 4-year-old children enrolled in a longitudinal study in Uganda. We found that repeated malaria was associated with reduced percentages of Vd2(+) ?d T cells in peripheral blood, decreased proliferation and cytokine production in response to malaria antigens, and increased expression of immunoregulatory genes. Further, loss and dysfunction of proinflammatory Vd2(+) ?d T cells were associated with a reduced likelihood of symptoms upon subsequent P. falciparum infection. Together, these results suggest that repeated malaria infection during childhood results in progressive loss and dysfunction of Vd2(+) ?d T cells that may facilitate immunological tolerance of the parasite.

View details for DOI 10.1126/scitranslmed.3009793

View details for PubMedID 25163477

View details for PubMedCentralID PMC4198150