Altered distributions and functions of natural killer T cells and γδ T cells in neonates with neonatal encephalopathy, in school-age children at follow-up, and in children with cerebral palsy

J Neuroimmunol. 2021 Jul 15:356:577597. doi: 10.1016/j.jneuroim.2021.577597. Epub 2021 Apr 29.


We enumerated conventional and innate lymphocyte populations in neonates with neonatal encephalopathy (NE), school-age children post-NE, children with cerebral palsy and age-matched controls. Using flow cytometry, we demonstrate alterations in circulating T, B and natural killer cell numbers. Invariant natural killer T cell and Vδ2+ γδ T cell numbers and frequencies were strikingly higher in neonates with NE, children post-NE and children with cerebral palsy compared to age-matched controls, whereas mucosal-associated invariant T cells and Vδ1 T cells were depleted from children with cerebral palsy. Upon stimulation ex vivo, T cells, natural killer cells and Vδ2 T cells from neonates with NE more readily produced inflammatory cytokines than their counterparts from healthy neonates, suggesting that they were previously primed or activated. Thus, innate and conventional lymphocytes are numerically and functionally altered in neonates with NE and these changes may persist into school-age.

Keywords: Cerebral palsy; Cytokines; Lymphocytes; Natural killer T cells; Neonatal encephalopathy; γδ T cells.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases / blood*
  • Brain Diseases / diagnosis*
  • Brain Diseases / immunology
  • Cerebral Palsy / blood*
  • Cerebral Palsy / diagnosis*
  • Cerebral Palsy / immunology
  • Child
  • Female
  • Follow-Up Studies
  • Humans
  • Infant, Newborn
  • Male
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / blood*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Students
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism


  • Receptors, Antigen, T-Cell, gamma-delta