Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice

Douglas A. Jabs, C. Lynne Burek, Qile Hu, Rudolf C. Kuppers, Bella Lee, Robert A. Prendergast

Research output: Contribution to journalArticle

Abstract

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. The target organ inflammatory lesions are composed largely of CD4+ "helper" T cells, while the massively enlarged lymph nodes are composed primarily of CD3+ CD4- CD8- TCR α β+ "double-negative" T cells. In this study we investigated the effect of treatment of MRL/lpr mice with antiCD4 monoclonal antibody (mAb); control groups consisted of animals treated with normal saline or rat immunoglobulin (Ig). Anti-CD4 mAb treatment, which was started at 4 weeks and continued through 20 weeks of age, resulted in a dramatic reduction of both the frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Anti-CD4 mAb therapy markedly reduced the frequency of glomerulonephritis and eliminated vasculitis of the major renal arterial branches. Glomerulonephritis was detected in 9 of 9 saline-treated, 9 of 9 rat Igtreated, but in only 1 of 9 anti-CD4 mAb-treated mice; vasculitis was detected in 6 of 9 salinetreated, 7 of 9 rat Ig-treated, but in none of 9 anti-CD4 mAb-treated mice. The frequency of antinuclear antibodies, titer of anti-dsDNA antibodies, and total Ig levels were all significantly reduced by anti-CD4 mAb therapy. These data support the hypothesis that CD4+ T cells play a central role in the disease process in this autoimmune strain.

Original languageEnglish (US)
Pages (from-to)496-507
Number of pages12
JournalCellular Immunology
Volume141
Issue number2
DOIs
StatePublished - May 1992

ASJC Scopus subject areas

  • Immunology

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