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

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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
Volume87
Issue number1
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Inbred MRL lpr Mouse
Autoimmunity
T-Lymphocytes
Nephritis
Lymphoproliferative Disorders
Vasculitis
Systemic Lupus Erythematosus
Autoantibodies
Autoimmune Diseases
Immunoglobulins
Spleen
Lymph Nodes
Kidney
Antibodies
DNA

Keywords

  • Autoimmunity
  • MRL/lpr mice
  • Murine lupus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

Cite this

Enhanced lymphoproliferation and diminished autoimmunity in CD4- deficient MRL/lpr mice. / Chestnutt, Mark; Finck, Barbara K.; Killeen, Nigel; Connolly, M. Kari; Goodman, Harris; Wofsy, David.

In: Clinical Immunology and Immunopathology, Vol. 87, No. 1, 01.01.1998, p. 23-32.

Research output: Contribution to journalArticle

Chestnutt, Mark ; Finck, Barbara K. ; Killeen, Nigel ; Connolly, M. Kari ; Goodman, Harris ; Wofsy, David. / Enhanced lymphoproliferation and diminished autoimmunity in CD4- deficient MRL/lpr mice. In: Clinical Immunology and Immunopathology. 1998 ; Vol. 87, No. 1. pp. 23-32.
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