Frequent Malaria Drives Progressive Vδ2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood

J Infect Dis. 2016 May 1;213(9):1483-90. doi: 10.1093/infdis/jiv600. Epub 2015 Dec 13.

Abstract

γδ T cells expressing Vδ2 may be instrumental in the control of malaria, because they inhibit the replication of blood-stage parasites in vitro and expand during acute malaria infection. However, Vδ2 T-cell frequencies and function are lower among children with heavy prior malaria exposure. It remains unclear whether malaria itself is driving this loss. Here we measure Vδ2 T-cell frequency, cytokine production, and degranulation longitudinally in Ugandan children enrolled in a malaria chemoprevention trial from 6 to 36 months of age. We observed a progressive attenuation of the Vδ2 response only among children incurring high rates of malaria. Unresponsive Vδ2 T cells were marked by expression of CD16, which was elevated in the setting of high malaria transmission. Moreover, chemoprevention during early childhood prevented the development of dysfunctional Vδ2 T cells. These observations provide insight into the role of Vδ2 T cells in the immune response to chronic malaria.

Keywords: CD16; Plasmodium falciparum; immunologic tolerance; malaria; γδ T cells.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artemisinins / administration & dosage
  • Child, Preschool
  • Drug Combinations
  • GPI-Linked Proteins / immunology
  • Humans
  • Immune Tolerance
  • Infant
  • Longitudinal Studies
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / prevention & control*
  • Plasmodium falciparum / immunology*
  • Pyrimethamine / administration & dosage
  • Quinolines / administration & dosage
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, IgG / immunology*
  • Sulfadoxine / administration & dosage
  • T-Lymphocyte Subsets / immunology*
  • Up-Regulation / immunology*

Substances

  • Artemisinins
  • Drug Combinations
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Quinolines
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, IgG
  • fanasil, pyrimethamine drug combination
  • dihydroartemisinin
  • Sulfadoxine
  • piperaquine
  • Pyrimethamine