The involvement of V(alpha)14 natural killer T cells in the pathogenesis of arthritis in murine models.
OBJECTIVE
To examine the physiologic role of natural killer T (NKT) cells bearing V(alpha)14 T cell receptor (TCR) in the pathogenesis of collagen-induced arthritis (CIA) and antibody-induced arthritis in mice.


METHODS
NKT cells were stained with alpha-galactosylceramide-loaded CD1 dimer, and then assessed using flow cytometry. CIA was induced in mice by immunization on days 0 and 21 with type II collagen (CII) emulsified with an equal volume of Freund's complete adjuvant. Anti-CII antibodies were measured by enzyme-linked immunosorbent assay. For antibody-induced arthritis, mice were injected with anti-CII monoclonal antibodies (mAb) followed by lipopolysaccharide, or with serum from KRN TCR-transgenic mice crossed with nonobese diabetic mice (K/BxN). The severity of arthritis was monitored with a macroscopic scoring system.


RESULTS
The number of NKT cells increased in the liver at the peak of the clinical course of CIA. Administration of anti-CD1 mAb inhibited development of CIA. The severity of CIA in NKT cell-deficient mice was reduced compared with that in wild-type mice. The IgG1:IgG2a ratio of anti-CII was elevated and production of interleukin-10 from draining lymph node cells was increased in NKT cell-deficient mice. NKT cell-deficient mice were significantly less susceptible to antibody-induced arthritis.


CONCLUSIONS
NKT cells contribute to the pathogenesis of arthritis by enhancing autoantibody-mediated inflammation. NKT cells also contribute to the disease process in a deleterious way, due, at least in part, to the alteration of the Th1/Th2 balance in T cell response to CII.
Chiba
Asako
A
National Institute of Neuroscience, Tokyo, Japan.
Kaieda
Shinjiro
S
Oki
Shinji
S
Yamamura
Takashi
T
Miyake
Sachiko
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000209:etiology / Q000276:immunology*; D024043:Collagen Type II / Q000009:adverse effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D023421:Models, Animal; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D024043:Collagen Type II