T-cells expressing natural killer (NK) receptors are altered in multiple sclerosis and responses to alpha-galactosylceramide are impaired

J Neurol Sci. 2008 Dec 15;275(1-2):22-8. doi: 10.1016/j.jns.2008.07.007. Epub 2008 Aug 15.


Multiple sclerosis (MS) is an autoimmune disorder characterised by clinical relapse and remission and pathological demyelination with varying inflammation. Because it is suggested that T-cells expressing natural killer cell receptors (NKR) play important roles in regulating human autoimmune diseases, we have quantified populations of T-cells expressing the NKR CD56, CD161 and CD94 in the peripheral blood of MS patients, in healthy control subjects (HS) and in patients with other neurological diseases (OND). CD161(+) T-cells and CD94(+) T-cells were significantly decreased in MS patients with primary progressive disease and secondary progressive disease respectively whereas CD56(+) T-cell numbers were unchanged. In contrast NKT-cells that express the invariant Valpha24-Jalpha18(+) T-cell receptor identified here by specific receptor antibody and CD1d-tetrameric PBS57-loaded complexes, were increased in MS patients compared with HS. Reductions in CD161(+) T-cells and CD94(+) T-cells relative to HS were also observed in the OND group and this was particularly prominent in Parkinsonian patients. A striking functional finding was that while NKT-cells in unfractionated peripheral blood from healthy subjects expanded in number and produced IFN-gamma upon stimulation with alpha-galactosylceramide, NKT-cells from MS patients did not. Thus we have identified alterations in a number of potentially important lymphocyte sub-populations warranting further investigation in the immune response in MS.

Publication types

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

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Disease Progression
  • Female
  • Flow Cytometry / methods
  • Galactosylceramides / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / pathology*
  • Natural Killer T-Cells / drug effects*
  • Nervous System Diseases / complications
  • Nervous System Diseases / pathology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Natural Killer Cell / metabolism*
  • Statistics, Nonparametric
  • Young Adult


  • Antigens, CD
  • Galactosylceramides
  • Receptors, Antigen, T-Cell
  • Receptors, Natural Killer Cell
  • Valpha24 protein, human
  • alpha-galactosylceramide