Chronic in vivo depletion of CD4 T cells increases both serum IgM levels and the expressed frequency of anti-ssDNA precursors in both NZB and DBA/2 mice.
Chronic depletion of CD4 T cells has been employed as therapy in a number of models of autoimmune disease, including spontaneously autoimmune NZB/W mice. In the present study, we evaluated the influence of CD4 depletion on the production of IgM and IgM anti-ssDNA. Beginning at 8 weeks of age, NZB and DBA/2 mice received 12 weekly injections of monoclonal antibody GK1.5 (anti-CD4) or normal rat IgG. In both strains, CD4 T cell depletion resulted in an increase in serum IgM. Anti-ssDNA precursors, which are increased in NZB mice, were further increased by depletion of CD4 T cells. The DBA/2 mouse expresses anti-ssDNA precursors relatively infrequently; however, CD4 T cell depletion resulted in a significant increase in the expression of these autoantibody precursors as well as an increase in the RNA content of splenic B cells. These results indicate that although CD4 T cell depletion ameliorates clinical manifestations of autoimmunity in some situations, this treatment may also increase serum IgM levels and the production of anti-ssDNA autoantibodies.
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
J S
JS
Cowdery
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology*; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D011498:Protein Precursors / Q000096:biosynthesis*; D012313:RNA / Q000032:analysis
D001323:Autoantibodies; D004277:DNA, Single-Stranded; D007075:Immunoglobulin M; D011498:Protein Precursors; D012313:RNA