Low levels of soluble CD1d protein alters NKT cell function in patients with rheumatoid arthritis.
CD1d molecules on the cell surface play a critical role in the presentation of glycolipid antigens to natural killer T (NKT) cells. We previously showed that the human CD1d gene has 8 splice variants, one of which is a soluble form lacking the beta2-m and transmembrane domains. This study focused on soluble CD1d (sCD1d) by generating recombinant sCD1d proteins and assaying them in plasma using a newly established ELISA method. The amount of sCD1d proteins in plasma was significantly decreased in rheumatoid arthritis (RA) patients (55.2+/-13.3 years, mean +/-SD) compared with healthy donors (31.2+/-7.4 years). Plasma sCD1d protein levels correlated with the number of NKT cells (TCR V alpha 24+ V beta 11+CD3+) in peripheral blood mononuclear cells (r(2)=0.061). Furthermore, sCD1d proteins induced IFN-gamma production from NKT cells, but neither IL-4 nor IL-10. These findings suggest that the low plasma levels of sCD1d protein in RA patients reduce the number and thus activation of peripheral NKT cells. It is therefore hypothesized that sCD1d stimulates NKT cells and low plasma sCD1d levels in RA reflect a pathogenic mechanism associated with a decrease in NKT cells.
Segawa
Seiji
S
Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
Goto
Daisuke
D
Yoshiga
Yohei
Y
Hayashi
Taichi
T
Matsumoto
Isao
I
Ito
Satoshi
S
Sumida
Takayuki
T
D000328:Adult; D000368:Aged; D055610:Antigens, CD1d / Q000097:blood* / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
D055610:Antigens, CD1d; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma