Effect of anti-CD4 antibody treatment on inflammatory arthritis in MRL-lpr/lpr mice.
MRL-lpr/lpr mice develop an inflammatory arthritis in association with other manifestations of autoimmunity. Although a variety of immune cell disturbances have been described in these mice, the relationship of these abnormalities to the pathogenesis of arthritis has not yet been determined; the role of T cells is especially unclear since synovial hypertrophy and joint erosions have been noted in some studies in the absence of a significant T cell infiltrate. Therefore, to determine if T cells are required for arthritis in MRL-lpr/lpr mice, we evaluated the effects of prolonged treatment with a monoclonal anti-CD4 antibody. Knee joints from treated mice had markedly reduced arthritis compared to saline-treated control animals as measured by the degree of synovial hypertrophy and inflammation. Nephritis in these mice was concomitantly reduced. In contrast, rheumatoid factor levels were not affected by CD4+ cell depletion, despite significant effects on anti-DNA. These results indicate that in MRL-lpr/lpr mice anti-CD4 therapy can inhibit arthritis, suggesting an important role of T cells in the pathogenesis of this lesion.
Medical Research Service, Durham VA Hospital, North Carolina.
G S
GS
Gilkeson
R
R
Spurney
T M
TM
Coffman
R
R
Kurlander
P
P
Ruiz
D S
DS
Pisetsky
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology; D007719:Knee Joint / Q000473:pathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012217:Rheumatoid Factor / Q000097:blood
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D007074:Immunoglobulin G; D004247:DNA; D012217:Rheumatoid Factor