Burel, Julie G., Apte, Simon H., Groves, Penny L., Klein, Kerenaftali, McCarthy, James S., and Doolan, Denise L. (2016) Reduced plasmodium parasite burden associates with CD38(+) CD4(+) T cells displaying cytolytic potential and impaired IFN-gamma production. PLoS Pathogens, 12 (9). pp. 1-22.

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Abstract

Using a unique resource of samples from a controlled human malaria infection ( CHMI) study, we identified a novel population of CD4(+) T cells whose frequency in the peripheral blood was inversely correlated with parasite burden following P. falciparum infection. These CD4(+) T cells expressed the multifunctional ectoenzyme CD38 and had unique features that distinguished them from other CD4(+) T cells. Specifically, their phenotype was associated with proliferation, activation and cytotoxic potential as well as significantly impaired production of IFN-gamma and other cytokines and reduced basal levels of activated STAT1. A CD38(+) CD4(+) T cell population with similar features was identified in healthy uninfected individuals, at lower frequency. CD38(+) CD4(+) T cells could be generated in vitro from CD38(-) CD4(+) T cells after antigenic or mitogenic stimulation. This is the first report of a population of CD38(+) CD4(+) T cells with a cytotoxic phenotype and markedly impaired IFN-gamma capacity in humans. The expansion of this CD38(+) CD4(+) T population following infection and its significant association with reduced blood-stage parasite burden is consistent with an important functional role for these cells in protective immunity to malaria in humans. Their ubiquitous presence in humans suggests that they may have a broad role in host-pathogen defense.

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