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
| Autor: | Oliver A. Garden, Flavia Rovis, Marina Botto, Robert I. Lechler, Clare R. Monk, Eva Leung, M Spachidou |
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| Rok vydání: | 2005 |
| Předmět: |
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 |
| Zdroj: | Arthritis and rheumatism. 52(4) |
| ISSN: | 0004-3591 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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