Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells.
In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation, and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.
Ezaki
I
I
Department of Clinical Immunology, Kyushu University, Beppu, Oita, Japan.
Okada
M
M
Yoshikawa
Y
Y
Fujikawa
Y
Y
Hashimoto
M
M
Otsuka
M
M
Nomura
T
T
Yamamoto
K
K
Watanabe
T
T
Shingu
M
M
Nobunaga
M
M
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002358:Cartilage, Articular / Q000473:pathology; D002455:Cell Division; D003094:Collagen / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007249:Inflammation; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D012217:Rheumatoid Factor / Q000008:administration & dosage / Q000494:pharmacology*; D012883:Skin Ulcer / Q000473:pathology; D013583:Synovial Membrane / Q000473:pathology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003094:Collagen; D012217:Rheumatoid Factor