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Loss and dysfunction of Vδ2⁺ γδ T cells are associated with clinical tolerance to malaria.
- Source :
-
Science translational medicine [Sci Transl Med] 2014 Aug 27; Vol. 6 (251), pp. 251ra117. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014, American Association for the Advancement of Science.)
- Subjects :
- Child
Child, Preschool
Cohort Studies
Gene Expression Profiling
Humans
Immunity
Immunomodulation
Incidence
Infant
Malaria, Falciparum epidemiology
Malaria, Falciparum genetics
Parasitemia immunology
Plasmodium falciparum immunology
T-Lymphocytes immunology
Treatment Outcome
Uganda epidemiology
Immune Tolerance immunology
Malaria, Falciparum immunology
Receptors, Antigen, T-Cell, gamma-delta immunology
T-Lymphocytes metabolism
T-Lymphocytes pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 6
- Issue :
- 251
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25163477
- Full Text :
- https://doi.org/10.1126/scitranslmed.3009793