IFNγ/IL-10 Co-producing Cells Dominate the CD4 Response to Malaria in Highly Exposed Children

PLoS Pathogens

Jordan W. Tappero¹  Moses R. Kamya²  Grant Dorsey³  Prasanna Jagannathan³  Ijeoma Eccles-James³  Jessica Briggs³  Katherine Bowen³  Bryan Greenhouse³  Margaret E. Feeney³  Emmanuel Arinaitwe⁴  Felistas Nankya⁴  Mary K. Muhindo⁴  Ann Auma⁴  Samuel Wamala⁴  Charles Ebusu⁴ 

[1] Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America;Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, United States of America;Infectious Diseases Research Collaboration, Kampala, Uganda

关键词: Malaria;    T cells;    Malarial parasites;    Cytokines;    Parasitemia;    Cell-mediated immunity;    Children;    Infectious disease control;   

DOI  :  10.1371/journal.ppat.1003864

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Although evidence suggests that T cells are critical for immunity to malaria, reliable T cell correlates of exposure to and protection from malaria among children living in endemic areas are lacking. We used multiparameter flow cytometry to perform a detailed functional characterization of malaria-specific T cells in 78 four-year-old children enrolled in a longitudinal cohort study in Tororo, Uganda, a highly malaria-endemic region. More than 1800 episodes of malaria were observed in this cohort, with no cases of severe malaria. We quantified production of IFNγ, TNFα, and IL-10 (alone or in combination) by malaria-specific T cells, and analyzed the relationship of this response to past and future malaria incidence. CD4+ T cell responses were measurable in nearly all children, with the majority of children having CD4+ T cells producing both IFNγ and IL-10 in response to malaria-infected red blood cells. Frequencies of IFNγ/IL10 co-producing CD4+ T cells, which express the Th1 transcription factor T-bet, were significantly higher in children with ≥2 prior episodes/year compared to children with <2 episodes/year (P<0.001) and inversely correlated with duration since malaria (Rho = −0.39, P<0.001). Notably, frequencies of IFNγ/IL10 co-producing cells were not associated with protection from future malaria after controlling for prior malaria incidence. In contrast, children with <2 prior episodes/year were significantly more likely to exhibit antigen-specific production of TNFα without IL-10 (P = 0.003). While TNFα-producing CD4+ T cells were not independently associated with future protection, the absence of cells producing this inflammatory cytokine was associated with the phenotype of asymptomatic infection. Together these data indicate that the functional phenotype of the malaria-specific T cell response is heavily influenced by malaria exposure intensity, with IFNγ/IL10 co-producing CD4+ T cells dominating this response among highly exposed children. These CD4+ T cells may play important modulatory roles in the development of antimalarial immunity.

【 授权许可】

CC BY