scholarly journals The Role of Different Subsets of Regulatory T Cells in Immunopathogenesis of Rheumatoid Arthritis

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Maryam Gol-Ara ◽  
Farhad Jadidi-Niaragh ◽  
Reza Sadria ◽  
Gholamreza Azizi ◽  
Abbas Mirshafiey
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Joint Inflammation ◽  
Frequency Function ◽  
Systemic Inflammatory Disease ◽  
Progression Of Disease ◽  
Cartilage Erosion ◽  
And Function

Rheumatoid arthritis (RA) is a common autoimmune disease and a systemic inflammatory disease which is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion and hyperplasia of synovial tissues. Considering the role of autoreactive T cells (particularly Th1 and Th17 cells) in pathophysiology of RA, it might be assumed that the regulatory T cells (Tregs) will be able to control the initiation and progression of disease. The frequency, function, and properties of various subsets of Tregs including natural Tregs (nTregs), IL-10-producing type 1 Tregs (Tr1 cells), TGF-β-producing Th3 cells, CD8+ Tregs, and NKT regulatory cells have been investigated in various studies associated with RA and collagen-induced arthritis (CIA) as experimental model of this disease. In this paper, we intend to submit the comprehensive information about the immunobiology of various subsets of Tregs and their roles and function in immunopathophysiology of RA and its animal model, CIA.

CD101 Expression and Function in Normal and Rheumatoid Arthritis-affected Human T Cells and Monocytes/Macrophages

2010 ◽  
Vol 38 (3) ◽  
pp. 419-428 ◽  
Author(s):  
DRAGAN V. JOVANOVIC ◽  
LAURENCE BOUMSELL ◽  
ARMAND BENSUSSAN ◽  
XAVIER CHEVALIER ◽  
ARTURO MANCINI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Map Kinase ◽  
Surface Expression ◽  
P38 Map Kinase ◽  
Autoimmune Response ◽  
Human Immune System ◽  
Kinase Activation ◽  
And Function

Objective.It was recently reported that CD101 surface expression discriminates potency among CD4+CD25+ FoxP3+ regulatory T cells in the mouse. We investigated whether CD101 may also have a role in the suppressor function of regulatory T cells in humans given that the latter population may affect the autoimmune response in patients with rheumatoid arthritis (RA).Methods.Sorted T cells and monocyte/macrophage cell populations were analyzed by flow cyto metry using conjugated antibodies specific for cell-surface markers. T cell proliferation assays were conducted by [3H]thymidine incorporation and CD8highcytotoxicity measurements by Cyto-Scan-LDH cytotoxicity assays. ELISA were used to measure cytokines in cell culture supernatants and Western blotting was performed for profiling mitogen-activated protein (MAP) kinase activation using specific antiphospholipid antibodies.Results.CD101 expression coincided with PMA-induced monocyte/leukocyte lineage differentiation. CD8highCD101− T cells exhibited greater cytotoxic activity than CD8highCD101+ T cells, while no difference was observed between CD4CD25highCD101+ and CD4CD25highCD101− Treg inhibitory activity through responder T cells. LPS-induced proinflammatory cytokine production and p38 MAP kinase activation were made possible by ligation of CD101 with an anti-CD101 antibody F(ab’)2fragment.Conclusion.These results suggested a modulatory/coregulatory function of CD101 in the human immune system, in contrast to murine models, in which CD101 surface expression discriminates potency among FoxP3+ regulatory T cells. Cytotoxic CD8highCD101+ T cells were markedly less cytotoxic than CD8highT cells negative for the CD101 antigen and were conspicuously downregulated in patients with RA, suggesting a possible role for CD101 expression and function in the control of certain manifestations of RA pathology.

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

2004 ◽  
Vol 200 (3) ◽  
pp. 277-285 ◽  
Author(s):  
Michael R. Ehrenstein ◽  
Jamie G. Evans ◽  
Animesh Singh ◽  
Samantha Moore ◽  
Gary Warnes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Significant Rise ◽  
Activated T Cells ◽  
Reactive Protein ◽  
Suppressive Phenotype ◽  
Factor Α

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.

The role of miR-155 in regulatory T cells and rheumatoid arthritis

2013 ◽  
Vol 148 (1) ◽  
pp. 56-65 ◽  
Author(s):  
D. Spoerl ◽  
I. Duroux-Richard ◽  
P. Louis-Plence ◽  
C. Jorgensen
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells

scholarly journals Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis

2010 ◽  
Vol 1 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Alessia Alunno ◽  
Elena Bartoloni ◽  
Giuseppe Nocentini ◽  
Onelia Bistoni ◽  
Simona Ronchetti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells

scholarly journals Expanding Regulatory T Cells Alleviates Chikungunya Virus-Induced Pathology in Mice

2015 ◽  
Vol 89 (15) ◽  
pp. 7893-7904 ◽  
Author(s):  
Wendy W. L. Lee ◽  
Teck-Hui Teo ◽  
Zhisheng Her ◽  
Fok-Moon Lum ◽  
Yiu-Wing Kam ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Chikungunya Virus ◽  
Interleukin 2 ◽  
Joint Inflammation ◽  
Chikv Infection ◽  
Joint Pathology ◽  
Alternative Approach ◽  
Control Virus

ABSTRACTChikungunya virus (CHIKV) infection is a reemerging pandemic human arboviral disease. CD4+T cells were previously shown to contribute to joint inflammation in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL-2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology. It does so by inhibiting the infiltration of CD4+T cells due to the induction of anergy in CHIKV-specific CD4+effector T cells. These findings suggest that activation of Tregs could also become an alternative approach to control CHIKV-mediated disease.IMPORTANCEChikungunya virus (CHIKV) has reemerged as a pathogen of global significance. Patients infected with CHIKV suffer from incapacitating joint pain that severely affects their daily functioning. Despite the best efforts, treatment is still inadequate. While T cell-mediated immunopathology in CHIKV infections has been reported, the role of regulatory T cells (Tregs) has not been explored. The JES6-1 anti-interleukin 2 (IL-2) antibody has been demonstrated to selectively expand mouse Tregs by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology in mice by neutralizing virus-specific CD4+effector T (Teff) cells. We show that this treatment abrogates the infiltration of pathogenic CD4+T cells through induction of anergy in CHIKV-specific CD4+Teff cells. This is the first evidence where the role of Tregs is demonstrated in CHIKV pathogenesis, and its expansion could control virus-mediated immunopathology.

The Role of Regulatory T Cells in Rheumatoid Arthritis

2002 ◽  
Vol 103 (s47) ◽  
pp. 32P-32P
Author(s):  
CA Lawson ◽  
F Ponchel ◽  
AW Boylston ◽  
P Emery ◽  
JD Isaacs
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells
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