Loss and dysfunction of Vδ2⁺ γδ T cells are associated with clinical tolerance to malaria.
Prasanna Jagannathan,Charles C. Kim,Bryan Greenhouse,Felistas Nankya,Katherine Bowen,Ijeoma Eccles-James,Mary K. Muhindo,Emmanuel Arinaitwe,Jordan W. Tappero,Moses R. Kamya,Grant Dorsey,Margaret E. Feeney +11 more
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TLDR
It is suggested 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.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 naive 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.read more
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Challenges and strategies for developing efficacious and long-lasting malaria vaccines
James G. Beeson,James G. Beeson,James G. Beeson,Liriye Kurtovic,Liriye Kurtovic,Carlota Dobaño,D. Herbert Opi,D. Herbert Opi,Jo-Anne Chan,Gaoqian Feng,Gaoqian Feng,Michael F. Good,Linda Reiling,Michelle J. Boyle +13 more
TL;DR: Greater knowledge of mechanisms and key targets of immunity are needed to accomplish this goal, together with new strategies for generating potent, long-lasting, functional immunity against multiple antigens.
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γδ T cells in tissue physiology and surveillance.
TL;DR: The roles of γδ T cells in tissue homeostasis and in surveillance of infection are reviewed, aiming to illustrate their major impact on tissue integrity, tissue repair and immune protection.
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T cell-mediated immunity to malaria
TL;DR: Current understanding of the mechanisms by which T cell subsets orchestrate host resistance to Plasmodium infection is reviewed on the basis of observational and mechanistic studies in humans, non-human primates and rodent models.
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FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.
Richard T. Sullivan,Charles C. Kim,Mary F. Fontana,Margaret E. Feeney,Prasanna Jagannathan,Michelle J. Boyle,Chris Drakeley,Isaac Ssewanyana,Felistas Nankya,Harriet Mayanja-Kizza,Grant Dorsey,Bryan Greenhouse +11 more
TL;DR: FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum, which is similar to dysfunctional B cells found in HIV-infected individuals.
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TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets.
Miguel Muñoz-Ruiz,Miguel Muñoz-Ruiz,Julie C. Ribot,Ana Rita Grosso,Natacha Gonçalves-Sousa,Ana Pamplona,Daniel J. Pennington,José R. Regueiro,Edgar Fernández-Malavé,Bruno Silva-Santos +9 more
TL;DR: TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory γδ T cell subsets and their impact on pathophysiology.
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