Sporici R A, Beswick R L, von Allmen C, Rumbley C A, Hayden-Ledbetter M, Ledbetter J A, Perrin P J
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Clin Immunol. 2001 Sep;100(3):277-88. doi: 10.1006/clim.2001.5074.
The interaction of ICOS with its ligand on APC provides a costimulatory signal to previously activated T-cells. In these studies, we blocked the ICOS:ICOS ligand interaction with ICOS-Ig during the in vitro activation of MBP-reactive transgenic CD4(+) T-cells. The presence of ICOS-Ig in these cultures inhibited the ability of the transgenic T-cells to transfer EAE, although they entered the brains of the recipient mice. ICOS-Ig increased apoptosis in the transgenic T-cells, especially in the memory population. This enhanced apoptosis was accompanied by an increase in the BAX/BCL-2 mRNA ratio. ICOS-Ig did not prevent IL2 production, demonstrating that IL-2 production is ICOS ligand independent. IFN-gamma and IL-10 production by the transgenic T-cells, however, was suppressed. Finally, ICOS-Ig injection into mice after the first signs of EAE ameliorated clinical disease. Therefore, ICOSL provides a signal distinct from CD28 costimulation that is required for the activation and viability of encephalitogenic T-cells.
ICOS与其在抗原呈递细胞（APC）上的配体相互作用，为先前活化的T细胞提供共刺激信号。在这些研究中，我们在髓鞘碱性蛋白（MBP）反应性转基因CD4(+) T细胞的体外活化过程中，用ICOS-Ig阻断ICOS与ICOS配体的相互作用。这些培养物中ICOS-Ig的存在抑制了转基因T细胞转移实验性自身免疫性脑脊髓炎（EAE）的能力，尽管它们进入了受体小鼠的大脑。ICOS-Ig增加了转基因T细胞的凋亡，尤其是在记忆细胞群体中。这种增强的凋亡伴随着BAX/BCL-2 mRNA比值的增加。ICOS-Ig并不阻止IL2的产生，表明IL-2的产生不依赖ICOS配体。然而，转基因T细胞产生的干扰素-γ（IFN-γ）和白细胞介素-10（IL-10）受到抑制。最后，在EAE出现最初症状后向小鼠注射ICOS-Ig可改善临床疾病。因此，ICOS配体（ICOSL）提供了一种不同于CD28共刺激的信号，该信号是致脑炎性T细胞活化和存活所必需的。
