CD4+CD25+ regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid
Abstract
AbstractObjectiveIn mice, CD4+CD25+ regulatory T cells play a pivotal role in preventing autoimmunity. Regulatory T cells are also present and functional in healthy humans. We investigated the presence, phenotype, and function of CD4+CD25+ regulatory T cells in peripheral blood (PB) and synovial fluid (SF) from patients with rheumatoid arthritis (RA).MethodsThe presence and phenotype of CD4+CD25+ regulatory T cells were determined by flow cytometry. Anergy and suppressive activity were assessed by culturing CD4+CD25− and CD4+CD25+ T cells with anti‐CD3 monoclonal antibodies and antigen‐presenting cells, followed by proliferation and cytokine detection.ResultsThe percentage of CD4+CD25+ T cells in RA SF was significantly increased compared with that in RA PB, and both of these percentages were higher than that in PB from controls. The cells in RA PB were similar in phenotype and function to CD4+CD25+ regulatory T cells from controls. In SF, however, ∼40–50% of CD4+CD25+ T cells expressed an activated phenotype, i.e., CD69+, class II MHC+, OX‐40+, with high levels of CTLA‐4 and glucocorticoid‐induced tumor necrosis factor receptor. These synovial CD4+CD25+ T cells displayed an increased suppressive capacity compared with blood CD4+CD25+ T cells. However, this enhanced suppressive activity was counterbalanced, because activated responder T cells from SF were less susceptible to CD4+CD25+ T cell–mediated suppression than were responder cells from PB.ConclusionWe demonstrate that CD4+CD25+ regulatory T cells are present and functional in patients with RA, with higher numbers of regulatory T cells with increased suppressive activity found in SF compared with PB. These findings suggest a negative feedback system that is active at the site of inflammation. The balance between activated responder and regulatory T cells appears to influence the extent of immunoregulation in RA.
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Cited By (18)
- The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitisJournal of Neuroimmunology · 2007
- Adaptive Foxp3+ regulatory T cell-dependent and –independent control of allergic inflammationImmunity · 2008
- The inflamed central nervous system drives the activation and rapid proliferation of Foxp3+ regulatory T cellsThe Journal of Immunology · 2007
- Proinflammatory mediator-induced reversal of CD4+CD25+ regulatory T cell-mediated suppression in rheumatoid arthritisArthritis & Rheumatism · 2007
- Function and Role of Regulatory T Cells in Rheumatoid ArthritisFrontiers in Immunology · 2021
- Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthmaJournal of Allergy and Clinical Immunology · 2007
- Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver
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