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

PLoS Pathogens

Denise L. Doolan¹  Penny L. Groves²  Julie G. Burel²  Kerenaftali Klein²  James S. McCarthy³  Simon H. Apte⁴ 

[1] Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia;Molecular Vaccinology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia;Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia;The University of Queensland, School of Medicine, Brisbane, Australia

关键词: T cells;    Parasitic diseases;    Cytokines;    Flow cytometry;    Malarial parasites;    Cell staining;    Plasmodium;    Malaria;   

DOI  :  10.1371/journal.ppat.1005839

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY