Effector functions of donor-reactive CD8 memory T cells are dependent on ICOS induced during division in cardiac grafts.
Effector functions of donor-reactive CD8 memory T cells are dependent on ICOS induced during division in cardiac grafts.
复制标题
DOI：
10.1111/j.1600-6143.2008.02460.x
复制
发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Valujskikh A
中科院分区：
文献类型：
--
作者：
Schenk AD;Gorbacheva V;Rabant M;Fairchild RL;Valujskikh A
同种异体反应性T细胞记忆存在于每个移植受体中，并危及移植物的存活。即使在没有已知的致敏暴露的情况下，异质性免疫和稳态T细胞增殖也产生具有供体反应性的“内源性”记忆T细胞。我们最近发现，内源性供体反应性CD 8记忆T细胞在再灌注数小时内浸润小鼠心脏移植物，并通过产生IFN-c放大移植后早期炎症。在这里，我们已经测试了ICOS共刺激在从这些记忆T细胞中激发效应子功能中的作用。ICOS在循环CD 8记忆T细胞的细胞表面上不表达，但在同种异体移植物实质内的细胞分裂期间迅速上调。供体反应性CD 8记忆T细胞浸润、增殖和ICOS表达受供体I类MHC分子表达调节。ICOS阻断显著降低了激活的CD 8记忆T细胞的IFN-c产生和其他促炎功能。我们的数据表明，外周组织内ICOS表达的这种诱导是CD 8记忆T细胞活化的重要特征，并将ICOS鉴定为中和内源性CD 8记忆T细胞的促炎功能的特异性靶标。
Alloreactive T-cell memory is present in every transplant recipient and endangers graft survival. Even in the absence of known sensitizing exposures, heterogonous immunity and homeostatic T-cell proliferation generate `endogenous' memory T cells with donor-reactivity. We have recently shown that endogenous donor-reactive CD8 memory T cells infiltrate murine cardiac allografts within hours of reperfusion and amplify early post-transplant inflammation by producing IFN-c. Here, we have tested the role of ICOS costimulation in eliciting effector function from these memory T cells. ICOS is not expressed on the cell surface of circulating CD8 memory T cells but is rapidly upregulated during cell division within the allograft parenchyma. Donor-reactive CD8 memory T-cell infiltration, proliferation and ICOS expression are regulated by donor class I MHC molecule expression. ICOS blockade significantly reduced IFN-c production and other proinflammatory functions of the activated CD8 memory T cells. Our data demonstrate that this induction of ICOS expression within peripheral tissues is an important feature of CD8 memory T-cell activation and identify ICOS as a specific target for neutralizing proinflammatory functions of endogenous CD8 memory T cells.
登录
查看更多内容
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
15.3
作者：
Herman, AE;Freeman, GJ;Benoist, C
通讯作者：
Benoist, C
影响因子：
5.4
作者：
Klingenberg, R;Autschbach, F;Dengler, TJ
通讯作者：
Dengler, TJ
影响因子：
6.2
作者：
Kosuge, H;Suzuki, JI;Uede, T
通讯作者：
Uede, T
影响因子：
64.8
作者：
Dong, C;Juedes, AE;Flavell, RA
通讯作者：
Flavell, RA