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Category: Data

Description: Repeated Plasmodium falciparum infections drive the development of clinical immunity to malaria in humans, however, the immunological mechanisms that underpin this response are only partially understood. Here, we investigated the impact of repeated P. falciparum infections on human γδ T cells in the context of natural infection in subjects from Mali and in a controlled human malaria infection (CHMI) of U.S. adults that established tolerance to malaria. In contrast to the predominant population of Vδ2+ γδ T cells in Australian individuals, we found that clonally expanded cytotoxic-Vδ1effector T cells were enriched in the γδ T cell compartment in subjects from Mali. Malaria-naïve U.S. adults exposed to four sequential CHMIs defined the precise impact of P. falciparum on the γδ T cell repertoire. Specifically, innate-like Vδ2+ γδ T cells initiated a robust polyclonal response to P. falciparum infection but this was not sustained with repeated infections, whereas Vδ1+ γδ T cells increased in frequency with repeated infections. Moreover, repeated P. falciparum drove waves of clonal selection in the Vδ1+ TCR repertoire that coincided with the differentiation of Vδ1naive cells into cytotoxic-Vδ1effector cells. Finally, Vδ1+ T cells from individuals with a history of prior exposure to P. falciparum from Mali or after CHMI were now licensed for reactivity to P. falciparum parasites in vitro. Together, our study indicates that repeated malaria drives the adaptive-like properties of the human γδ T cell repertoire and establishes a major component of the immune response to P. falciparum infection in vivo.