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PLoS Pathog ; 16(10): e1008997, 2020 10.
Article in English | MEDLINE | ID: mdl-33085728

ABSTRACT

Vγ9Vδ2 T cells rapidly respond to phosphoantigens produced by Plasmodium falciparum in an innate-like manner, without prior antigen exposure or processing. Vδ2 T cells have been shown to inhibit parasite replication in vitro and are associated with protection from P. falciparum parasitemia in vivo. Although a marked expansion of Vδ2 T cells is seen after acute malaria infection in naïve individuals, repeated malaria causes Vδ2 T cells to decline both in frequency and in malaria-responsiveness, and to exhibit numerous transcriptional and phenotypic changes, including upregulation of the Fc receptor CD16. Here we investigate the functional role of CD16 on Vδ2 T cells in the immune response to malaria. We show that CD16+ Vδ2 T cells possess more cytolytic potential than their CD16- counterparts, and bear many of the hallmarks of mature NK cells, including KIR expression. Furthermore, we demonstrate that Vδ2 T cells from heavily malaria-exposed individuals are able to respond to opsonized P.falciparum-infected red blood cells through CD16, representing a second, distinct pathway by which Vδ2 T cells may contribute to anti-parasite effector functions. This response was independent of TCR engagement, as demonstrated by blockade of the phosphoantigen presenting molecule Butyrophilin 3A1. Together these results indicate that Vδ2 T cells in heavily malaria-exposed individuals retain the capacity for antimalarial effector function, and demonstrate their activation by opsonized parasite antigen. This represents a new role both for Vδ2 T cells and for opsonizing antibodies in parasite clearance, emphasizing cooperation between the cellular and humoral arms of the immune system.


Subject(s)
Malaria, Falciparum/immunology , Malaria/immunology , Receptors, IgG/immunology , T-Lymphocytes/immunology , Adult , Child , Child, Preschool , Female , GPI-Linked Proteins/immunology , GPI-Linked Proteins/metabolism , Humans , Immunity , Infant , Malaria/blood , Malaria/parasitology , Malaria, Falciparum/metabolism , Malaria, Falciparum/parasitology , Male , Middle Aged , Parasitemia/immunology , Plasmodium falciparum/growth & development , Plasmodium falciparum/metabolism , Receptors, IgG/metabolism , T-Lymphocyte Subsets/immunology , T-Lymphocytes/metabolism , Uganda/epidemiology
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