Compromised Function of Regulatory T Cells in Rheumatoid Arthritis and Reversal by Anti-TNFα Therapy

By M. Ehrenstein, Jamie G. Evans, Animesh Singh, S. Moore, G. Warnes, D. Isenberg, C. Mauri. Journal of Experimental Medicine, 2004

1,246 citations recorded by the source corpus.

Regulatory T cells have been clearly implicated in the control of disease in murine models of autoimmunity. The paucity of data regarding the role of these lymphocytes in human autoimmune disease has prompted us to examine their function in patients with rheumatoid arthritis (RA). Regulatory (CD4+CD25+) T cells isolated from patients with active RA displayed an anergic phenotype upon stimulation with anti-CD3 and anti-CD28 antibodies, and suppressed the proliferation of effector T cells in vitro. However, they were unable to suppress proinflammatory cytokine secretion from activated T cells and monocytes, or to convey a suppressive phenotype to effector CD4+CD25− T cells. Treatment with antitumor necrosis factor α (TNFα; Infliximab) restored the capacity of regulatory T cells to inhibit cytokine production and to convey a suppressive phenotype to “conventional” T cells. Furthermore, anti-TNFα treatment led to a significant rise in the number of peripheral blood regulatory T cells in RA patients responding to this treatment, which correlated with a reduction in C reactive protein. These data are the first to demonstrate that regulatory T cells are functionally compromised in RA, and indicate that modulation of regulatory T cells by anti-TNFα therapy may be a further mechanism by which this disease is ameliorated.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/58bf18df93ad7bbe8d544a45c3101d8f759f8f3b

How researchers see this paper

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In Immunology

1. Shimon Sakaguchi
2. K. Wing
3. M. Miyara
4. Tomoyuki Yamaguchi
5. T. Nomura
6. M. Ono
7. C. Mauri
8. Georg Schett

Citations in the corpus

• CD19+CD24hiCD38hi B Cells Maintain Regulatory T Cells While Limiting TH1 and TH17 Differentiation (2013, background): “Indeed, the defective function of Tregs in patients with active RA suggests that an unbalanced Treg versus T helper 1 (TH1) and TH17 response may favor the pathogenesis of RA (14, 15).”
• Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. (2008, background): “The normal functions of Tregs, including the suppression of proinflammatory cytokine secretion by activated T cells and monocytes, are reduced in patients with RA compared with healthy individuals (Ehrenstein et al., 2004).”
• Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. (2009, background): “They play crucial roles in human diseases, such as autoimmune disease, allergy, and cancer (Curiel et al., 2004; Ehrenstein et al., 2004; Kriegel et al., 2004; Miyara et al., 2005; Viglietta et al., 2004).”
• CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. (2010, background): “Defects in regulatory T cells have been identified in several autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), and SLE (Ehrenstein et al., 2004; Viglietta et al., 2004).”
• Cytokines in the pathogenesis of rheumatoid arthritis (2007, background): “Naturally occurring T Reg cells (that is, the forkhead box P3 (FOXP3) + CD4 + CD25 + regulatory T-cell subset) have been detected in the synovium of patients with active disease and particularly in synovial fluid, but they seem to have impaired regulatory functio”