Role of IL-12 in overcoming the low responsiveness of NK cells to missing self after traumatic brain injury

Clin Immunol. 2017 Apr:177:87-94. doi: 10.1016/j.clim.2015.08.006. Epub 2015 Sep 24.

Abstract

Blood samples from 32 patients with severe Traumatic brain injury (TBI) were studied and compared with 11 cardiac surgery patients, and 29 healthy controls. A dramatic decreased expression of HLA class I molecules on monocytes was associated with increased KIR+ NK cell frequency in TBI patients. Overall, the phenotype of TBI NK cells marked by KIR and CD57 expression and lower level of NKp46 and DNAM-1 reflected a differentiated state. The NK-cell response to missing self was marked by lower degranulation and lower IFN-γ production after stimulation with HLA class I deficient cell line. In contrast, the NK-cell ADCC was not altered. IL-12 was able to restore both IFN-γ production and the cytotoxicity capacities of NK cells. This study provides the first extensive description of the phenotype and functions of NK cells in TBI patients. Further evaluation of IL-12 treatment to overcome immunosuppression-induced nosocomial infections is warranted.

Keywords: HLA class I; IL-12; Immune suppression; KIR; Monocytes; NK cells; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Injuries, Traumatic / immunology*
  • Cell Degranulation / immunology
  • Female
  • Genes, MHC Class I
  • Genes, MHC Class II
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology*
  • Killer Cells, Natural / immunology*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Interleukin-12
  • Interferon-gamma