Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation
Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation
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DOI：
10.1016/j.immuni.2006.04.015
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发表时间：
2006-07-01
期刊：
影响因子：
32.4
通讯作者：
von Andrian, Ulrich H.
中科院分区：
文献类型：
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作者：
Mempel, Thorsten R.;Pittet, Mikael J.;von Andrian, Ulrich H.
哺乳动物免疫系统中的显性耐受机制已经进化，以防止不适当的免疫反应。CD4(+)CD25(+)调节性T(T-reg)细胞已经成为这种抑制活动的中心成分。利用多光子活体显微镜观察麻醉小鼠的淋巴结(LNS)，我们分析了在存在或不存在激活的T-reg细胞的情况下，细胞毒性T淋巴细胞(CTL)如何与抗原提呈靶细胞相互作用。非受管制的CTL杀死目标的速度是受管制的CTL的6.6倍。尽管效应器活性受损，但受调控的CTL在增殖、诱导细胞毒效应分子和分泌颗粒、原位运动或与靶细胞形成抗原依赖偶联的能力方面没有缺陷。在T-reg细胞存在的情况下，只有CTL的颗粒胞吐功能明显受损。这种选择性的调节形式不需要CTL和T-reg细胞之间的长时间接触，而是依赖于CTL对转化生长因子-β的反应。选择性去除T-reg细胞后，CTL在LNS中迅速恢复完全杀伤能力。因此，T-reg细胞可逆地抑制CTL介导的免疫，允许获得全部效应器潜力，但不允许获得杀伤许可证。
Mechanisms of dominant tolerance have evolved within the mammalian immune system to prevent inappropriate immune responses. CD4(+)CD25(+) regulatory T (T-reg) cells have emerged as central constituents of this suppressive activity. By using multiphoton intravital microscopy in lymph nodes (LNs) of anesthetized mice, we have analyzed how cytotoxic T lymphocytes (CTLs) interact with antigen-presenting target cells in the presence or absence of activated T-reg cells. Nonregulated CTLs killed their targets at a 6.6-fold faster rate than regulated CTLs. In spite of this compromised effector activity, regulated CTLs exhibited no defect in proliferation, induction of cytotoxic effector molecules and secretory granules, in situ motility, or ability to form antigen-dependent conjugates with target cells. Only granule exocytosis by CTLs was markedly impaired in the presence of T-reg cells. This selective form of regulation did not require prolonged contact between CTLs and T-reg cells but depended on CTL responsiveness to transforming growth factor-beta. CTLs quickly regained full killing capacity in LNs upon selective removal of T-reg cells. Thus, T-reg cells reversibly suppress CTL-mediated immunity by allowing acquisition of full effector potential but withholding the license to kill.