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Reduced Plasmodium Parasite Burden Associates with CD38+ CD4+ T Cells Displaying Cytolytic Potential and Impaired IFN-γ Production.
- Source :
- PLoS Pathogens; 9/23/2016, Vol. 12 Issue 9, p1-22, 22p
- Publication Year :
- 2016
-
Abstract
- Using a unique resource of samples from a controlled human malaria infection (CHMI) study, we identified a novel population of CD4<superscript>+</superscript> T cells whose frequency in the peripheral blood was inversely correlated with parasite burden following P. falciparum infection. These CD4<superscript>+</superscript> T cells expressed the multifunctional ectoenzyme CD38 and had unique features that distinguished them from other CD4<superscript>+</superscript> 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<superscript>+</superscript> CD4<superscript>+</superscript> T cell population with similar features was identified in healthy uninfected individuals, at lower frequency. CD38<superscript>+</superscript> CD4<superscript>+</superscript> T cells could be generated in vitro from CD38<superscript>-</superscript> CD4<superscript>+</superscript> T cells after antigenic or mitogenic stimulation. This is the first report of a population of CD38<superscript>+</superscript> CD4<superscript>+</superscript> T cells with a cytotoxic phenotype and markedly impaired IFN-γ capacity in humans. The expansion of this CD38<superscript>+</superscript> CD4<superscript>+</superscript> 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 , and [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 12
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 118317617
- Full Text :
- https://doi.org/10.1371/journal.ppat.1005839