UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy

Ehrenstein, MR; Evans, JG; Singh, A; Moore, S; Warnes, G; Isenberg, DA; Mauri, C; (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy. J EXP MED , 200 (3) 277 - 285. 10.1084/jem.20040165. Green open access

[thumbnail of 7090.pdf]
Preview
PDF
7090.pdf

Download (242kB)

Abstract

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 alpha (TNFalpha; Infliximab) restored the capacity of regulatory T cells to inhibit cytokine production and to convey a suppressive phenotype to "conventional" T cells. Furthermore, anti-TNFalpha 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-TNFalpha therapy may be a further mechanism by which this disease is ameliorated.

Type: Article
Title: Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20040165
Keywords: T lymphocytes, tolerane, autoinimune disease, TNF alpha, cytokines, NECROSIS-FACTOR-ALPHA, EX-VIVO, BLOOD, TOLERANCE, INFLAMMATION, LYMPHOCYTES, SUPPRESSION, HOMEOSTASIS, THYMOCYTES, SYSTEM
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/7090
Downloads since deposit
394Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item