title: Effects of early and late treatment with anti-CD4 monoclonal antibody on autoimmune disease in MRL/MP-lpr/lpr mice.
abstract: MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop a systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation, with target organ inflammatory lesions composed largely of CD4+ (helper) T cells. Previous reports have demonstrated that anti-CD4 monoclonal antibody (mAb) treatment of MRL/lpr mice from 1 to 5 months of age resulted in a dramatic reduction in both the frequency and the severity of autoimmune disease. In order to investigate the effects of early, short-course and late, short-course anti-CD4 mAb therapy on the autoimmune disease in MRL/lpr mice, groups of 12 to 15 animals were treated with weekly intraperitoneal injections according to one of four regimens: (i) anti-CD4 mAb from age 1 to 5 months (continuous treatment); (ii) anti-CD4 mAb from age 1 to 3 months (early treatment); (iii) anti-CD4 mAb from age 3 to 5 months (late treatment); and (iv) either normal saline or rat immunoglobulin (control treatment). Continuous treatment resulted in a dramatic reduction of both frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Early treatment also resulted in a significant reduction in autoimmune disease, while late treatment had little effect. Glomerulonephritis was detected in none of the animals in the continuously treated group (P < 0.05), 38% of those in the early-treated group (P = < 0.05), 92% of the late-treated group, and 100% of controls. The titer of antinuclear antibodies, of anti-dsDNA antibodies, and total immunoglobulin levels were all significantly reduced in the continuous-treatment and early-treatment groups, but not in the late-treatment group. Murine antibodies to rat anti-CD4 mAb were present in the late-treatment group. These results indicate that early short-course anti-CD4 mAb treatment of MRL/lpr mice is effective in ameliorating the autoimmune disease in this model, while late-treatment is ineffective, probably due to the induction of antibody directed against anti-CD4 mAb itself.
authors.affiliation: Wilmer Ophthalmological Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: D A
authors.initials: DA
authors.lastname: Jabs
authors.forename: R C
authors.initials: RC
authors.lastname: Kuppers
authors.forename: A M
authors.initials: AM
authors.lastname: Saboori
authors.forename: C L
authors.initials: CL
authors.lastname: Burek
authors.forename: C
authors.initials: C
authors.lastname: Enger
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.forename: R A
authors.initials: RA
authors.lastname: Prendergast
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001327:Autoimmune Diseases / Q000235:genetics / Q000517:prevention & control* / Q000628:therapy; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002455:Cell Division; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D051381:Rats; D013997:Time Factors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G