Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy.
Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy.
复制标题
调节性T细胞在类风湿关节炎和抗TNFALPHA治疗中的逆转功能受损。
DOI：
10.1084/jem.20040165
复制
发表时间：
2004-08-02
影响因子：
15.3
通讯作者：
Mauri, C
中科院分区：
文献类型：
--
作者：
Ehrenstein, MR;Evans, JG;Singh, A;Moore, S;Warnes, G;Isenberg, DA;Mauri, C
调节性T细胞已明确涉及在自身免疫的鼠模型中的疾病控制。关于这些淋巴细胞在人类自身免疫性疾病中的作用的数据的缺乏促使我们检查它们在类风湿性关节炎（RA）患者中的功能。从活动性RA患者中分离的调节性（CD 4 + CD 25+）T细胞在抗CD 3和抗CD 28抗体刺激后表现出无反应性表型，并抑制效应T细胞的体外增殖。然而，它们不能抑制活化T细胞和单核细胞的促炎细胞因子分泌，也不能将抑制性表型传递给效应CD 4 + CD 25 − T细胞。抗肿瘤坏死因子α（TNFα;英夫利昔单抗）治疗恢复了调节性T细胞抑制细胞因子产生的能力，并将抑制性表型传递给“常规”T细胞。此外，抗TNF α治疗导致RA患者外周血调节性T细胞数量显著增加，这与C反应蛋白降低相关。这些数据首次证明了RA中调节性T细胞的功能受损，并表明抗TNF α治疗对调节性T细胞的调节可能是改善该疾病的进一步机制。
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.
登录
查看更多内容
DOI：
10.1084/jem.193.11.1303
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者：
Schuler G
DOI：
10.1084/jem.20020394
发表时间：
2002-07-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jonuleit H;Schmitt E;Kakirman H;Stassen M;Knop J;Enk AH
通讯作者：
Enk AH
影响因子：
27.4
作者：
Swaak, AJG;vandenBrink, HG;Aarden, LA
通讯作者：
Aarden, LA
DOI：
10.1073/pnas.172382999
发表时间：
2002-09-17
影响因子：
11.1
作者：
Wu, AJ;Hua, H;McDevitt, HO
通讯作者：
McDevitt, HO
DOI：
10.1084/jem.20020110
发表时间：
2002-08-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Liotta F;Lazzeri E;Manetti R;Vanini V;Romagnani P;Maggi E;Romagnani S
通讯作者：
Romagnani S