Age-related changes in PD-1 expression coincide with increased cytotoxic potential in Vδ2 T cells during infancy

Cell Immunol. 2021 Jan:359:104244. doi: 10.1016/j.cellimm.2020.104244. Epub 2020 Nov 13.

Abstract

Human Vγ9Vδ2 T cells respond to several diverse pathogens by sensing microbial cholesterol intermediates. Unlike CD4 T cells, they are poised for rapid Th1-like responses even before birth, which allows them to play a key role in the first line of defense against pathogens in early life. However, their regulation and functional maturation during infancy (in particular the acquisition of cytotoxic potential) remain understudied. We thus characterized their responses to cholesterol intermediates and Bacille Calmette-Guérin in a cohort of African neonates and 12-month-old infants. Infant Vδ2 lymphocytes exhibited intermediate or adult-like expression of markers associated with differentiation or function, intermediate proliferative responses, and adult-like cytotoxic potential. The enhancement of Vδ2 cell cytotoxic potential coincided with decreasing PD-1 and increasing NKG2A expression. Our results are consistent with the hypothesis that switching from a PD-1+ to a NKG2A+ phenotype during infancy indicates a shift in mechanisms regulating Vδ2 T cell function.

Keywords: BCG; Cord blood; Cytotoxic potential; Gammadelta T cells; Infant; PD-1.

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cordocentesis
  • Female
  • Fetal Blood / cytology*
  • Gene Expression / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / immunology
  • Malawi / epidemiology
  • Male
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Lymphocytes / immunology

Substances

  • KLRC1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell, gamma-delta
  • Interferon-gamma