ICOS ligand costimulation is required for T-cell encephalitogenicity.
ICOS ligand costimulation is required for T-cell encephalitogenicity.
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DOI：
10.1006/clim.2001.5074
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发表时间：
2001-09
影响因子：
8.6
通讯作者：
R. Sporici;Richard L. Beswick;C. Allmen;C. A. Rumbley;M. Hayden-Ledbetter;J. Ledbetter;P. Perrin
中科院分区：
文献类型：
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作者：
R. Sporici;Richard L. Beswick;C. Allmen;C. A. Rumbley;M. Hayden-Ledbetter;J. Ledbetter;P. Perrin
ICOS 与其 APC 上的配体相互作用，为先前激活的 T 细胞提供共刺激信号。在这些研究中，我们在MBP反应性转基因CD4(+) T细胞的体外激活过程中阻断了ICOS:ICOS配体与ICOS-Ig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 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，尤其是记忆细胞群。这种细胞凋亡的增强伴随着 BAX/BCL-2 mRNA 比率的增加。 ICOS-Ig 不会阻止 IL2 的产生，表明 IL-2 的产生与 ICOS 配体无关。然而，转基因T细胞产生的IFN-γ和IL-10受到抑制。最后，在出现 EAE 最初迹象后，将 ICOS-Ig 注射到小鼠体内可改善临床疾病。因此，ICOSL 提供了与 CD28 共刺激不同的信号，该信号是致脑炎 T 细胞的激活和活力所必需的。
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.