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Loss and dysfunction of V?2? ?? T cells are associated with clinical tolerance to malaria.

ABSTRACT: Although clinical immunity to malaria eventually develops among children living in endemic settings, the underlying immunologic mechanisms are not known. The V?2(+) subset of ?? 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 ?? 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 V?2(+) ?? 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 V?2(+) ?? 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 V?2(+) ?? T cells that may facilitate immunological tolerance of the parasite.

SUBMITTER: Jagannathan P

PROVIDER: S-EPMC4198150 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Jagannathan Prasanna P Kim Charlie C CC Greenhouse Bryan B Nankya Felistas F Bowen Katherine K Eccles-James Ijeoma I Muhindo Mary K MK Arinaitwe Emmanuel E Tappero Jordan W JW Kamya Moses R MR Dorsey Grant G Feeney Margaret E ME

Science translational medicine 20140801 251

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 mala ...[more]

PMID: 25163477

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Loss and dysfunction of V?2? ?? T cells are associated with clinical tolerance to malaria.

Publications

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

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