Disparate T cell requirements of two subsets of lupus-specific autoantibodies in pristane-treated mice.
Intraperitoneal injection of pristane induces a lupus-like disease in BALB/c and other non-autoimmune mice characterized by autoantibody production and the development of immune complex disease closely resembling lupus nephritis. Two subsets of autoantibodies are induced by pristane: IgG anti-DNA DNA and -chromatin autoantibodies are strongly IL-6-dependent, whereas IgG anti-nRNP/Sm and -Su antibodies are not. The present studies were carried out to examine the role of T cells in establishing this dichotomy between the production of anti-nRNP/Sm/Su versus anti-DNA/chromatin autoantibodies. Autoantibody production and renal disease were evaluated in athymic (nude) mice treated with pristane. BALB/c nu/nu mice spontaneously developed IgM and IgG anti-single-stranded (ss)DNA and -chromatin, but not anti-nRNP/Sm or -Su, autoantibodies. Pristane treatment increased the levels of IgG anti-chromatin antibodies in nu/nu mice, but did not induce production of anti-nRNP/Sm or -Su antibodies. In contrast, BALB/c nu/+ and +/+ control mice did not spontaneously produce autoantibodies, whereas anti-nRNP/Sm and -Su autoantibodies were induced by pristane in approx. 50% of nu/+ and +/+ mice and anti-DNA/chromatin antibodies at lower frequencies. Nude mice spontaneously developed mild renal lesions that were marginally affected by pristane, but were generally milder than the lesions developing in pristane-treated nu/+ and +/+ mice. The data provide further evidence that two distinct pathways with different cytokine and T cell requirements are involved in autoantibody formation in pristane-induced lupus. This dichotomy may be relevant to understanding differences in the regulation of anti-DNA versus anti-nRNP/Sm autoantibodies in systemic lupus erythematosus, as well as the association of anti-DNA, but not anti-nRNP/Sm, with lupus nephritis.
Richards
H B
HB
Department of Medicine and Microbiology/Immunology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill 27599-7280, USA.
Satoh
M
M
Jennette
J C
JC
Okano
T
T
Kanwar
Y S
YS
Reeves
W H
WH
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis* / Q000145:classification*; D001324:Autoantigens; D002843:Chromatin / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007105:Immune Complex Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011506:Proteins / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear; D013601:T-Lymphocytes / Q000276:immunology*; D013729:Terpenes / Q000633:toxicity; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D002843:Chromatin; D004277:DNA, Single-Stranded; D011506:Proteins; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; C089635:Su autoantigen; D013729:Terpenes; D055517:snRNP Core Proteins; C009042:pristane