Treatment of a newly established transgenic model of chronic arthritis with nondepleting anti-CD4 monoclonal antibody.
We established a novel animal model for rheumatoid arthritis (RA) by following backcrossing to DBA/1 of (SWR/J x DBA/1)F1 TCR-beta Tg mice, previously reported to be highly susceptible to collagen-induced arthritis. These mice evolved, upon collagen type II immunization, into a chronic arthritis that histopathologically resembles RA. The availability of such a model prompted us to study the role of CD4+ T cells throughout the evolution of disease. Here, we show that administration of nondepleting anti-CD4 not only prevented the evolution of disease but also treated established arthritis. Moreover, functional analyses of T cells isolated from anti-CD4-treated mice demonstrated that the mechanism of protection is not achieved by suppression of the Th1 population but is mediated by induction of collagen type II-specific T cell anergy. Our study suggests that: 1) CD4+ T cells have a fundamental role both in the induction and in the perpetuation of disease; 2) targeting T cells may be an appropriate therapeutic option; and 3) a suitable and well-balanced anti-CD4 treatment may be a valid approach to the control of RA.
Mauri
C
C
Immunology Division, Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom.
Chu
C Q
CQ
Woodrow
D
D
Mori
L
L
Londei
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology*; D003094:Collagen / Q000276:immunology / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D000939:Epitopes; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen