Deletion, but not anergy, is involved in TGF-beta-treated antigen-presenting cell-induced tolerance.
Deletion, but not anergy, is involved in TGF-beta-treated antigen-presenting cell-induced tolerance.
复制标题
TGF-β处理的抗原呈递细胞诱导的耐受性涉及缺失，但不涉及无反应性。
DOI：
10.1093/intimm/mcg092
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发表时间：
2003
影响因子：
4.4
通讯作者：
Kosiewicz,MicheleM
中科院分区：
文献类型：
--
作者：
Alard,Pascale;Clark,SherryL;Kosiewicz,MicheleM
静脉注射经抗原脉冲处理的转化生长因子 (TGF-)-β 处理的抗原呈递细胞 (APC)，可在首次接触的小鼠和先前引发的小鼠中诱导抗原特异性耐受。尽管 TGF-β 处理的 APC 诱导的耐受性与调节性 T 细胞的诱导和迟发型超敏反应 (DTH) 反应受损有关，但介导这种耐受性的具体机制目前尚不清楚。本报告的目的是通过确定受调节的抗原特异性效应 T 细胞的命运来研究 TGF-β 处理的 APC 诱导的耐受性的机制。使用一个能够追踪少量 TCR 转基因 T 细胞的充分表征的系统，我们发现在注射 TGF-β 处理的 APC 的小鼠体内或体外，抗原特异性 T 细胞的扩增受到抑制。抗原特异性效应T细胞扩增失败似乎并不是由于无反应性的诱导，因为羧基荧光素二乙酸琥珀酰亚胺酯（CFSE）标记的细胞在体内响应抗原和佐剂而正常分裂，并且添加外源IL-2无法在体外测定中恢复T细胞扩增。有趣的是，体外培养后，CFSE 标记细胞的百分比在> 7-8 次分裂后下降，这与细胞死亡的显着增加相关。通过抗 Fas 配体 (FasL) 抗体处理，可以防止细胞死亡并恢复体外扩增的能力。总之，TGF-β处理的 APC 诱导的耐受似乎与涉及 Fas-FasL 途径的抗原特异性 T 细胞的缺失有关。
Intravenous injection of transforming growth factor (TGF‐)‐β‐treated antigen‐presenting cells (APC) pulsed with antigen induces antigen‐specific tolerance in both naive and previously primed mice. Although TGF‐β‐treated APC‐induced tolerance is associated with induction of regulatory T cells and impaired delayed‐type hypersensitivity (DTH) responses, the specific mechanisms that mediate this tolerance are not currently known. The goal of the present report was to study the mechanisms involved in TGF‐β‐treated APC‐induced tolerance by determining the fate of the antigen‐specific effector T cells that are regulated. Using a well‐characterized system that allows tracking of small numbers of TCR transgenic T cells, we have found that antigen‐specific T cell expansion, eitherin vivoorin vitro, is inhibited in mice that have been injected with TGF‐β‐treated APC. The failure of antigen‐specific effector T cells to expand did not appear to be due to the induction of anergy, since carboxyfluorescein diacetate succinimidyl ester (CFSE)‐labeled cells divided normally in response to antigen and adjuvantin vivo, and addition of exogenous IL‐2 was unable to restore T cell expansion inin vitroassays. Interestingly, the percentage of CFSE‐labeled cells was decreased after >7–8 divisions following culturein vitro, which correlated with a significant increase in cell death. Cell death was prevented and the ability to expandin vitrowas restored by treatment with anti‐Fas ligand (FasL) antibody. In conclusion, tolerance induced by TGF‐β‐treated APC appears to be associated with deletion of antigen‐specific T cells involving the Fas–FasL pathway.