1. 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
- Author
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Oliver A. Garden, Flavia Rovis, Marina Botto, Robert I. Lechler, Clare R. Monk, Eva Leung, and M Spachidou
- Subjects
medicine.medical_specialty ,Mice, Inbred MRL lpr ,T cell ,Immunology ,chemical and pharmacologic phenomena ,Cell Count ,T-Lymphocytes, Regulatory ,Interleukin 21 ,Mice ,Rheumatology ,Species Specificity ,immune system diseases ,T-Lymphocyte Subsets ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,IL-2 receptor ,skin and connective tissue diseases ,Cells, Cultured ,business.industry ,CD28 ,Peripheral tolerance ,hemic and immune systems ,Receptors, Interleukin-2 ,T lymphocyte ,Flow Cytometry ,Molecular biology ,In vitro ,Coculture Techniques ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,Self Tolerance ,Monoclonal ,business - Abstract
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.
- Published
- 2005