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gammadelta T cells expressing Vdelta2 may be instrumental in the control of malaria, as they inhibit the replication of blood-stage parasites in vitro and expand during acute malaria infection. However, Vdelta2 T cell frequencies and function are lower among children with heavy prior malaria exposure. It remains unclear whether malaria itself is driving this loss. Here we measure Vdelta2 T cell frequency, cytokine production, and degranulation longitudinally in Ugandan children enrolled in a malaria chemoprevention trial from 6 to 36 months of age. We observed a progressive attenuation of the Vdelta2 response only among children incurring high rates of malaria. Unresponsive Vdelta2 T-cells were marked by expression of CD16, which was elevated in the setting of high malaria transmission. Moreover, chemoprevention during early childhood prevented the development of dysfunctional Vdelta2 T cells. These observations provide insight into the role of Vdelta2 T cells in the immune response to chronic malaria.
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