Evidence for an Adult-Like Type 1-Immunity Phenotype of Vδ1, Vδ2 and Vδ3 T Cells in Ghanaian Children With Repeated Exposure to Malaria

Abstract

Effector capabilities of γδ T cells are evident in <i>Plasmodium</i> infection in young and adult individuals, while children are the most vulnerable groups affected by malaria. Here, we aimed to investigate the age-dependent phenotypic composition of Vδ1⁺, Vδ2⁺, and Vδ3⁺ T cells in children living in endemic malaria areas and how this differs between children that will develop symptomatic and asymptomatic <i>Plasmodium falciparum</i> infections. Flow cytometric profiling of naïve and effector peripheral blood γδ T cells was performed in 6 neonates, 10 adults, and 52 children. The study population of young children, living in the same malaria endemic region of Ghana, was monitored for symptomatic <i>vs</i> asymptomatic malaria development for up to 42 weeks after peripheral blood sampling at baseline. For the Vδ2⁺ T cell population, there was evidence for an established type 1 effector phenotype, characterized by CD94 and CD16 expression, as early as 1 year of life. This was similar among children diagnosed with symptomatic or asymptomatic malaria. In contrast, the proportion of type 2- and type 3-like Vδ2 T cells declined during early childhood. Furthermore, for Vδ1⁺ and Vδ3⁺ T cells, similar phenotypes of naïve (CD27⁺) and type 1 effector (CD16⁺) cells were observed, while the proportion of CD16⁺ Vδ1⁺ T cells was highest in children with asymptomatic malaria. In summary, we give evidence for an established adult-like γδ T cell compartment in early childhood with similar biology of Vδ1⁺ and Vδ3⁺ T cells. Moreover, the data supports the idea that type 1 effector Vδ1⁺ T cells mediate the acquisition of and can potentially serve as biomarker for natural immunity to <i>P. falciparum</i> infections in young individuals from malaria-endemic settings.