Reduced plasmodium parasite burden associates with CD38(+) CD4(+) T cells displaying cytolytic potential and impaired IFN-gamma production

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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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.

Item ID: 46388
Item Type: Article (Research - C1)
ISSN: 1553-7374
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© 2016 Burel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: Medicines for Malaria Venture, National Health and Medical Research Council (NHMRC), University of Queensland (UQ), Queensland Government
Projects and Grants: NHMRC Program Grant #1037304
Date Deposited: 16 Nov 2016 07:41
FoR Codes: 42 HEALTH SCIENCES > 4206 Public health > 420699 Public health not elsewhere classified @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 25%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320405 Humoural immunology and immunochemistry @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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