Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells

Nat Med. 2008 Mar;14(3):337-42. doi: 10.1038/nm1715. Epub 2008 Feb 17.


Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system (CNS) characterized by a wide range of clinical signs. The location of lesions in the CNS is variable and is a crucial determinant of clinical outcome. Multiple sclerosis is believed to be mediated by myelin-specific T cells, but the mechanisms that determine where T cells initiate inflammation are unknown. Differences in lesion distribution have been linked to the HLA complex, suggesting that T cell specificity influences sites of inflammation. We demonstrate that T cells that are specific for different myelin epitopes generate populations characterized by different T helper type 17 (T(H)17) to T helper type 1 (T(H)1) ratios depending on the functional avidity of interactions between TCR and peptide-MHC complexes. Notably, the T(H)17:T(H)1 ratio of infiltrating T cells determines where inflammation occurs in the CNS. Myelin-specific T cells infiltrate the meninges throughout the CNS, regardless of the T(H)17:T(H)1 ratio. However, T cell infiltration and inflammation in the brain parenchyma occurs only when T(H)17 cells outnumber T(H)1 cells and trigger a disproportionate increase in interleukin-17 expression in the brain. In contrast, T cells showing a wide range of T(H)17:T(H)1 ratios induce spinal cord parenchymal inflammation. These findings reveal critical differences in the regulation of inflammation in the brain and spinal cord.

Publication types

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

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Brain / cytology
  • Brain / metabolism
  • Central Nervous System / cytology
  • Central Nervous System / immunology*
  • Epitopes / immunology
  • Epitopes / metabolism
  • Gene Expression Regulation
  • Mice
  • Mice, Inbred Strains
  • Specific Pathogen-Free Organisms
  • Spinal Cord / cytology
  • Spinal Cord / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Epitopes