Journal Article

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

Doolan, Denise L., Klein, Kerenaftali, Burel, Julie G., Apte, Simon H., Groves, Penny L., McCarthy, James S.

2016

Overview

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. ClinicalTrials.gov clinical trial numbers ACTRN12612000814875, ACTRN12613000565741 and ACTRN12613001040752.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ADP-ribosyl Cyclase 1 - metabolism / Adult / Biology and Life Sciences / CD4 Lymphocyte Count / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - metabolism / CD4-Positive T-Lymphocytes - pathology / Cell Count / Cytotoxicity, Immunologic / Healthy Volunteers / Humans / Interferon-gamma - metabolism / Lymphocyte Activation / Malaria, Falciparum - immunology / Malaria, Falciparum - metabolism / Malaria, Falciparum - parasitology / Malaria, Falciparum - pathology / Medicine and Health Sciences / Membrane Glycoproteins - metabolism / Parasitemia - immunology / Parasitemia - pathology / Plasmodium falciparum - immunology / Research and Analysis Methods