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 …
CR Monk, M Spachidou, F Rovis, E Leung… - Arthritis & …, 2005 - Wiley Online Library
CR Monk, M Spachidou, F Rovis, E Leung, M Botto, RI Lechler, OA Garden
Arthritis & Rheumatism, 2005•Wiley Online LibraryObjective 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 …
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 …
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.
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