每位移植受者均存在同种反应性T细胞的记忆性，对于移植物的存活率不利。甚至在不存在明确致敏状况的情况下，一种免疫以及自身内环境稳定的T细胞增殖产生的“内源性”记忆T细胞存在供者反应性。我们最近的研究显示小鼠心脏移植开放血流灌注后数小时内即出现内源性供者反应性CD8记忆T细胞的增殖以及产生IFN-gamma出现移植后早期炎症反应的扩大。我们检测了在引出这些记忆T细胞效应器功能中ICOS共刺激通路的作用。在循环CD8记忆T细胞的表明并没有ICOS的表达，但是其在移植物实质内细胞分化期间对其有正性调节作用。供者MHC-I类分子的表达能够调节供者反应性CD8记忆T细胞浸润、增殖以及ICOS的表达。ICOS信号的阻断能够显著降低IFN-gamma的产生以及活化的CD8记忆T细胞的其他促炎症功能。我们的数据提示外周组织ICOS表达的诱导是CD8记忆T细胞活化的特征，同时明确了ICOS是中和内源性CD8记忆T细胞促炎症功能的特殊靶位。

Schenk AD, Gorbacheva V, Rabant M, Fairchild RL, Valujskikh A.
Department of Pathology, Case Western Reserve University, Cleveland, OH.

Alloreactive T-cell memory is present in every transplant recipient and endangers graft survival. Even in the absence of known sensitizing exposures, heterologous 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 posttransplant inflammation by producing IFN-gamma. Here, we have tested the role of ICOS co-stimulation 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-gamma 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.