T cells are involved in the development of arthritis induced by anti-type II collagen antibody.
T cells play an important role in initiating autoimmune responses and maintaining synovial inflammation in rheumatoid arthritis. Although, anti-type II collagen antibody-induced arthritis (CAIA) is generally believed to be a T cell- and B cell-independent model, the detailed pathogenesis of CAIA remains unclear. In the present study, to elucidate the contribution of T cells to the pathogenesis of CAIA, we evaluated the effects of CTLA4 Ig and cyclosporin (CsA). Arthritis was induced in mice by intravenous injection of anti-type II collagen antibody followed by intraperitoneal injection of lipopolysaccharide. CTLA4 Ig was intraperitoneally administered and CsA was subcutaneously administered; then the severity of arthritis was evaluated by scoring the edema and erythema of paws and by measuring hind paw thickness. Paw samples were collected 12 days after the antibody injection, and the mRNA expression levels were analyzed by real-time quantitative polymerase chain reaction. Administration of CTLA4 Ig ameliorated the increases in arthritic score and paw thickness in the later phase, but not in the early phase of arthritis. CsA suppressed the increases in arthritic score and paw thickness in both the early and later phases of arthritis. CTLA4 Ig and CsA suppressed mRNA up-regulation of T-cell markers, CD3 and CD25, and immune response-related mediators, IFN-gamma and IL-12. They also suppressed the up-regulation of macrophage marker, F4/80, and proinflammatory cytokines, TNF-alpha, IL-1beta and IL-6. The results provide direct evidence that arthritis in this model is T-cell activation dependent.
Mitamura
Mana
M
GlaxoSmithKline Research and Development, Tsukuba Research Laboratories, Ibaraki, Japan.
Nakano
Nami
N
Yonekawa
Taeko
T
Shan
Lihua
L
Kaise
Toshihiko
T
Kobayashi
Tomohiro
T
Yamashita
Keizo
K
Kikkawa
Hideo
H
Kinoshita
Mine
M
D000069594:Abatacept; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics; D024043:Collagen Type II / Q000276:immunology*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D018796:Immunoconjugates / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
D017252:CD3 Complex; D024043:Collagen Type II; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D018664:Interleukin-12; D000069594:Abatacept; D007371:Interferon-gamma; D016572:Cyclosporine