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Sci Transl Med. 2014 Aug 27;6(251):251ra117. doi: 10.1126/scitranslmed.3009793.

Loss and dysfunction of Vδ2⁺ γδ T cells are associated with clinical tolerance to malaria.

Author information

1
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94110, USA.
2
Infectious Diseases Research Collaboration, P.O. Box 7475, Kampala, Uganda.
3
Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
4
Department of Medicine, Makerere University College of Health Sciences, P.O. Box 7051, Kampala, Uganda.
5
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94110, USA. Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94110, USA. margaret.feeney@ucsf.edu.

Abstract

Although clinical immunity to malaria eventually develops among children living in endemic settings, the underlying immunologic mechanisms are not known. The Vδ2(+) subset of γδ T cells have intrinsic reactivity to malaria antigens, can mediate killing of Plasmodium falciparum merozoites, and expand markedly in vivo after malaria infection in previously naïve hosts, but their role in mediating immunity in children repeatedly exposed to malaria is unclear. We evaluated γδ T cell responses to malaria among 4-year-old children enrolled in a longitudinal study in Uganda. We found that repeated malaria was associated with reduced percentages of Vδ2(+) γδ T cells in peripheral blood, decreased proliferation and cytokine production in response to malaria antigens, and increased expression of immunoregulatory genes. Further, loss and dysfunction of proinflammatory Vδ2(+) γδ T cells were associated with a reduced likelihood of symptoms upon subsequent P. falciparum infection. Together, these results suggest that repeated malaria infection during childhood results in progressive loss and dysfunction of Vδ2(+) γδ T cells that may facilitate immunological tolerance of the parasite.

PMID:
25163477
PMCID:
PMC4198150
DOI:
10.1126/scitranslmed.3009793
[Indexed for MEDLINE]
Free PMC Article

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