MRL/Mp CD4+,CD25- T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythematosus

Arthritis Rheum. 2005 Apr;52(4):1180-4. doi: 10.1002/art.20976.


Objective: To investigate the hypothesis that loss of suppression mediated by peripheral CD4+,CD25+ regulatory T cells is a hallmark of systemic lupus erythematosus (SLE).

Methods: Mice of the MRL/Mp strain were studied as a polygenic model of SLE. Following immunomagnetic selection, peripheral lymphoid CD25+ and CD25- CD4+ T cells were cultured independently or together in the presence of anti-CD3/CD28 monoclonal antibody-coated beads. Proliferation was assessed by measuring the incorporation of tritiated thymidine.

Results: While MRL/Mp CD4+,CD25+ regulatory T cells showed only subtle abnormalities of regulatory function in vitro, syngeneic CD4+,CD25- T cells showed significantly reduced sensitivity to suppression, as determined by crossover experiments in which MRL/Mp CD4+,CD25- T cells were cultured with H-2-matched CBA/Ca CD4+,CD25+ regulatory T cells in the presence of a polyclonal stimulus.

Conclusion: Our findings highlight a novel defect of peripheral tolerance in SLE. Identification of this defect could open new opportunities for therapeutic intervention.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cells, Cultured
  • Coculture Techniques
  • Disease Models, Animal
  • Flow Cytometry
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology*
  • Mice
  • Mice, Inbred MRL lpr / genetics
  • Mice, Inbred MRL lpr / immunology*
  • Receptors, Interleukin-2 / immunology*
  • Self Tolerance / immunology*
  • Species Specificity
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / ultrastructure
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / ultrastructure


  • Receptors, Interleukin-2