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

MR Ehrenstein, JG Evans, A Singh, S Moore… - The Journal of …, 2004 - rupress.org
MR Ehrenstein, JG Evans, A Singh, S Moore, G Warnes, DA Isenberg, C Mauri
The Journal of experimental medicine, 2004rupress.org
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 …
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.
rupress.org