Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis.
Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis.
复制标题
DOI：
10.4049/jimmunol.182.3.1469
复制
发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
Whiteside TL
中科院分区：
文献类型：
--
作者：
Strauss L;Bergmann C;Whiteside TL
人类调节性T细胞(Treg)用于消除效应细胞的机制可能有所不同。我们探讨了Treg抑制的机制可能依赖于Fas/FasL介导的反应细胞(RC)的凋亡。从25例癌症患者和15例正常人外周血中分离出CD_4+CD_(25)−、Foxp_3+Treg和自体CD_4+CD_(25)−和CD_8+CD_(25)T细胞亚群，并与OKT_3和IL-2(150或1000IU/ml)共同培养。CFSE检测对RC增殖的抑制。7-氨基放线菌素D染色流式细胞仪检测RC和Treg细胞的凋亡情况。所有受试者的Treg均表达CD95+，但只有癌症患者的Treg表达CD95L。当这些Treg被Tcr和IL-2激活时，上调CD95L和CD95L的表达(p<；0.001)，并通过诱导Fas介导的凋亡抑制CD8+RC的增殖(p<；0.001)。然而，与CD4+RC共培养的Treg不依赖于Fas/FasL而抑制细胞增殖。在共培养中，当存在1000IU/mlIL-2时，Treg对凋亡具有抵抗作用，但当IL-2浓度较低时(150IU/ml)，Treg对RC诱导的死亡变得敏感。因此，Treg和RC可以相互调节Treg的存活，这取决于共培养中存在的IL-2浓度。这种不同的IL-2依赖的抗性或Treg和RC对凋亡的敏感性在癌症患者中被放大。
Mechanisms utilized by human regulatory T cells (Treg) for elimination of effector cells may vary. We investigated the possibility that the mechanism of Treg suppression depends on Fas/FasL-mediated apoptosis of responder cells (RC). CD4+CD25highFoxp3+Treg and autologous CD4+CD25− and CD8+CD25− subsets of RC were isolated from blood of 25 cancer patients and 15 normal controls and cocultured in the presence of OKT3 and IL-2 (150 or 1000 IU/ml). Suppression of RC proliferation was measured in CFSE assays. RC and Treg apoptosis was monitored by 7-aminoactinomycin D staining in flow-based cytotoxicity assays. Treg from all subjects expressed CD95+, but only Treg from cancer patients expressed CD95L. These Treg, when activated via TCR plus IL-2, up-regulated CD95 and CD95L expression (p < 0.001) and suppressed CD8+ RC proliferation (p < 0.001) by inducing Fas-mediated apoptosis. However, Treg cocultured with CD4+ RC suppressed proliferation independently of Fas/FasL. In co-cultures, Treg were found to be resistant to apoptosis in the presence of 1000 IU/ml IL-2, but at lower IL-2 concentrations (150 IU/ml) they became susceptible to RC-induced death. Thus, Treg and RC can reciprocally regulate Treg survival, depending on IL-2 concentrations present in cocultures. This divergent IL-2-dependent resistance or sensitivity of Treg and RC to apoptosis is amplified in patients with cancer.
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
人CD25（+）CD4（+）T调节细胞抑制幼稚和记忆T细胞增殖，可以在体外扩展而不会失去功能。
影响因子：
15.3
作者：
Levings, M K;Sangregorio, R;Roncarolo, M G
通讯作者：
Roncarolo, M G
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
8.6
作者：
Adriani, Marsilio;Aoki, Joseph;Schwartzberg, Pamela L.
通讯作者：
Schwartzberg, Pamela L.
影响因子：
11.5
作者：
Bergmann, Christoph;Strauss, Laura;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.