LONG-TERM ANTI-CD4 TREATMENT OF MRL/LPR MICE AMELIORATES IMMUNOPATHOLOGY AND LYMPHOPROLIFERATION BUT FAILS TO SUPPRESS RHEUMATOID-FACTOR PRODUCTION

MRL/ipr mice were treated with anti-CD4 mAb to define the role of CD4+ T cells in the pathogenesis of autoimmune disease and the lymphoproliferation characteristic of the strain. Anti-CD4 treatment was not associated with adverse effects, and survival of treated mice was increased over that of rat IgG-treated controls. Renal function was preserved, and the histologic severity of glomerulonephritis was minimal in treated mice. Lymphoid tissues of mice receiving anti-CD4 were effectively depleted of CD4+ T cells, and lymphoproliferation was markedly reduced. Serum IgG, anti-Sm, and anti-dsDNA levels were reduced significantly, while serum IgM and IgM rheumatoid factor levels were unaffected by anti-CD4 treatment. These data show that in MRL/Ipr mice lymphoproliferation, renal disease, anti-Sm and anti-dsDNA antibody production, and elevated IgG levels are all linked to CD4+ T cell function. In contrast, both total IgM and IgM rheumatoid factor production appear to be the result of B-cell activity that is not regulated by CD4+ T cells. © 1991 Academic Press, Inc.