Enhanced lymphoproliferation and diminished autoimmunity in CD4- deficient MRL/lpr mice

Mark S. Chesnutt, Barbara K. Finck, Nigel Killeen, M. Kari Connolly, Harris Goodman, David Wofsy

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


MRL/lpr mice spontaneously develop an autoimmune disease with features of systemic lupus erythematosus. They also develop a lymphoproliferative disorder characterized by a massive accumulation of double-negative (DN) T cells that lack both CD4 and CD8. To clarify the role of CD4 in autoimmunity and lymphoproliferation in these mice, CD4-deficient MRL/lpr mice were generated. CD4-deficient MRL/lpr mice developed massive expansion of DN T cells in the blood, spleen, and lymph nodes, which significantly exceeded the degree of lymphoproliferation in CD4-expressing control MRL/lpr mice. Despite this lymphoproliferation, CD4-deficient MRL/lpr mice produced little, if any, antibodies to double-stranded DNA, and they had prolonged survival relative to CD4-expressing littermates. However, they eventually developed moderately severe nephritis, characterized by immunoglobulin and complement deposition in glomeruli, vasculitis, and renal infiltration by CD8+ T cells. These findings indicate that (1) lymphoproliferation in lpr mice does not require the expression of CD4; (2) autoantibody production in MRL/lpr mice is dependent on the expression of CD4 and not on the accumulation of DN T cells; and (3) the development of nephritis in MRL/lpr mice involves both CD4- dependent and CD4-independent mechanisms.

Original languageEnglish (US)
Pages (from-to)23-32
Number of pages10
JournalClinical Immunology and Immunopathology
Issue number1
StatePublished - Apr 1998
Externally publishedYes


  • Autoimmunity
  • MRL/lpr mice
  • Murine lupus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology


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