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 [formula omitted] mice

Abstract

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.