The onset of nephritis in the (NZB x SWR)F1 murine model for systemic lupus erythematosus correlates with an increase in the ratio of CD4 to CD8 T lymphocytes specific for the nephritogenic idiotype (IdLNF1).
An idiotypically related family of nephritogenic antibodies (IdLNF1) has been shown to be important in the pathogenesis of autoimmune glomerulonephritis in the (NZB x SWR)F1 hybrid, SNF1. Idiotype-specific T lymphocytes which modulate expression of antibody bearing that idiotype may be important in the pathogenesis of systemic lupus erythematosus (SLE). Here, IdLNF1-reactive T lymphocytes were not only found to be present in the NZB, SWR, and SNF1, but a significantly (P < or = 0.05) greater number of IdLNF1-reactive Thy 1.2+ splenic lymphocytes were observed as early as 12 weeks of age in the SNF1. Further, a significant shift in the ratio of CD4+ to CD8+ IdLNF1-reactive T lymphocytes in favor of CD4+ IdLNF1-reactive T cells was observed at 20 to 24 weeks of age only in the SNF1. This shift correlated with an increase in IdLNF1+IgG, and deposition of IdLNF1 bearing immunoglobulin in the kidney glomeruli. These observations suggest a role for idiotype-specific T lymphocytes in the induction of glomerulonephritis in this murine model of SLE.
Knupp
C J
CJ
Department of Microbiology, SUNY-HSC, Syracuse 13210.
Uner
A H
AH
Tatum
A H
AH
Gavalchin
J
J
D000375:Aging / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis; D003429:Cross Reactions; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M / Q000096:biosynthesis; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008814:Mice, Inbred NZB; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018800:Thy-1 Antigens
D000974:Antibodies, Antinuclear; D000954:Antigens, Surface; D016827:CD8 Antigens; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens