Both MHC and non-MHC genes regulate inflammation and T-cell response after traumatic brain injury

Brain Behav Immun. 2011 Jul;25(5):981-90. doi: 10.1016/j.bbi.2010.10.017. Epub 2010 Oct 23.


Genetic regulation of autoimmune neuroinflammation is a well known phenomenon, but genetic influences on inflammation following traumatic nerve injuries have received little attention. In this study we examined the inflammatory response in a rat traumatic brain injury (TBI) model, with a particular focus on major histocompatibility class II (MHC II) presentation, in two inbred rat strains that have been extensively characterized in experimental autoimmune encephalomyelitis (EAE); DA and PVG. In addition, MHC and Vra4 congenic strains on these backgrounds were studied to give information on MHC and non-MHC gene contribution. Thus, allelic differences in Vra4, harboring the Ciita gene, was found to regulate expression of the invariant chain at the mRNA level, with a much smaller effect exerted by the MHC locus itself. Notably, however, at the protein level the MHC congenic PVG-RT1(av1) strain displayed much stronger MHCII(+) presentation, as shown both by immunolabeling and flow cytometry, than the PVG strain, dwarfing the effect of Ciita. The PVG-RT1(av1) strain had significantly more T-cell influx than both DA and PVG, suggesting regulation both by MHC and non-MHC genes. Finally, in terms of outcome, the EAE susceptible DA strain displayed a significantly smaller resulting lesion volume than the resistant PVG-RT1(av1) strain. These results provide additional support for a role of adaptive immune response after neurotrauma and demonstrate that outcome is significantly affected by host genetic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / immunology
  • Brain / pathology
  • Brain Injuries / immunology*
  • Brain Injuries / pathology
  • Flow Cytometry
  • Genes, MHC Class II / drug effects
  • Genes, MHC Class II / immunology
  • Genes, MHC Class II / physiology
  • Inflammation / immunology*
  • Inflammation / physiopathology
  • Major Histocompatibility Complex / drug effects
  • Major Histocompatibility Complex / immunology*
  • Major Histocompatibility Complex / physiology
  • Male
  • Myelin Basic Protein / pharmacology
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology


  • Myelin Basic Protein
  • Peptide Fragments
  • myelin basic protein 63-88