Opsonized antigen activates Vδ2+ T cells via CD16/FCγRIIIa in individuals with chronic malaria exposure

PLoS Pathog. 2020 Oct 21;16(10):e1008997. doi: 10.1371/journal.ppat.1008997. eCollection 2020 Oct.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • FCGR3A protein, human
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Receptors, IgG