Reduced Plasmodium Parasite Burden Associates with CD38+ CD4+ T Cells Displaying Cytolytic Potential and Impaired IFN-γ Production

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-γ 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-γ 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. trial registration: clinicaltrials.gov clinical trial numbers actrn12612000814875,actrn12613000565741 and actrn12613001040752 © 2016 burel et al.