Journal article
Chronic Exposure to Plasmodium falciparum Is Associated with Phenotypic Evidence of B and T Cell Exhaustion
The Journal of immunology (1950), Vol.190(3), pp.1038-1047
02/01/2013
DOI: 10.4049/jimmunol.1202438
PMCID: PMC3549224
PMID: 23264654
Abstract
Naturally acquired immunity to malaria develops slowly, requiring several years of repeated exposure to be effective. The cellular and molecular factors underlying this observation are only partially understood. Recent studies suggest that chronic
Plasmodium falciparum
exposure may induce functional exhaustion of lymphocytes, potentially impeding optimal control of infection. However, it remains unclear whether the “atypical” memory B cells (MBCs) and “exhausted” CD4 T cells described in humans exposed to endemic malaria are driven by
P. falciparum
per se or by other factors commonly associated with malaria, such as coinfections and malnutrition. To address this critical question we took advantage of a “natural” experiment near Kilifi, Kenya, and compared profiles of B and T cells of children living in a rural community where
P. falciparum
transmission is ongoing to the profiles of age-matched children living under similar conditions in a nearby community where
P. falciparum
transmission ceased 5 y prior to this study. We found that continuous exposure to
P. falciparum
drives the expansion of atypical MBCs. Persistent
P. falciparum
exposure was associated with an increased frequency of CD4 T cells expressing phenotypic markers of exhaustion, both programmed cell death-1 (PD-1) alone and PD-1 in combination with lymphocyte-activation gene-3 (LAG-3). This expansion of PD-1–expressing and PD-1/LAG-3–coexpressing CD4 T cells was largely confined to CD45RA
+
CD4 T cells. The percentage of CD45RA
+
CD27
+
CD4 T cells coexpressing PD-1 and LAG-3 was inversely correlated with frequencies of activated and classical MBCs. Taken together, these results suggest that
P. falciparum
infection per se drives the expansion of atypical MBCs and phenotypically exhausted CD4 T cells, which has been reported in other endemic areas.
Details
- Title: Subtitle
- Chronic Exposure to Plasmodium falciparum Is Associated with Phenotypic Evidence of B and T Cell Exhaustion
- Creators
- Joseph Illingworth - Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LJ, United KingdomNoah S Butler - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104Sophie Roetynck - Division of Parasitology, National Institute for Medical Research, London NW7 1AA, United Kingdom; andJedida Mwacharo - Kenya Medical Research Institute, Centre for Geographical Medicine Research (Coast), Kilifi, KenyaSusan K Pierce - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852Philip Bejon - Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LJ, United KingdomPeter D Crompton - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852Kevin Marsh - Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LJ, United KingdomFrancis M Ndungu - Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LJ, United Kingdom
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.190(3), pp.1038-1047
- DOI
- 10.4049/jimmunol.1202438
- PMID
- 23264654
- PMCID
- PMC3549224
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- AAI
- Language
- English
- Date published
- 02/01/2013
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002399502771
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