Long-term anti-CD4 treatment of MRL/lpr mice ameliorates immunopathology and lymphoproliferation but fails to suppress rheumatoid factor production.
MRL/lpr 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/lpr 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.
O'Sullivan
F X
FX
Section of Rheumatology, Harry S. Truman V.A. Medical Center, Columbia, Missouri.
Ray
C J
CJ
Takeda
Y
Y
Sharp
G C
GC
Walker
S E
SE
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology; D015704:CD4 Antigens / Q000276:immunology*; D002455:Cell Division; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007668:Kidney / Q000473:pathology / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D012217:Rheumatoid Factor / Q000096:biosynthesis*; D013997:Time Factors
D000906:Antibodies; D001323:Autoantibodies; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012217:Rheumatoid Factor