T-cells expressing natural killer (NK) receptors are altered in multiple sclerosis and responses to alpha-galactosylceramide are impaired.
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.
O'Keeffe
Joan
J
Department of Biochemistry, School of Natural Sciences, National University of Ireland Galway, Ireland. joan.okeeffe@nuigalway.ie
Gately
Carol M
CM
Counihan
Timothy
T
Hennessy
Michael
M
Leahy
Teresa
T
Moran
Anthony P
AP
Hogan
Edward L
EL
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005699:Galactosylceramides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology*; D055611:Natural Killer T-Cells / Q000187:drug effects*; D009422:Nervous System Diseases / Q000150:complications / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000378:metabolism*; D018709:Statistics, Nonparametric; D055815:Young Adult
D015703:Antigens, CD; D005699:Galactosylceramides; D011948:Receptors, Antigen, T-Cell; D055607:Receptors, Natural Killer Cell; C528689:Valpha24 protein, human; C493154:alpha-galactosylceramide