ICOS contributes to T cell expansion in CTLA-4 deficient mice
ICOS contributes to T cell expansion in CTLA-4 deficient mice
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DOI：
10.4049/jimmunol.175.1.182
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Oosterwegel, MA
中科院分区：
文献类型：
--
作者：
van Berkel, MEAT;Schrijver, EHR;Oosterwegel, MA
CD 28和ICOS都是重要的共刺激分子，促进Ag特异性细胞和体液免疫反应。尽管CD 28通常被认为是T细胞应答起始中最重要的分子，但ICOS被认为在效应期起作用。我们已经研究了在不存在CTLA-4介导的抑制的情况下ICOS对T细胞应答的贡献。缺乏CTLA-4的小鼠表现出自发的CD 28介导的CD 4（+）T细胞活化、扩增和分化，用拮抗性α ICOS抗体治疗。阻断ICOS与其配体B7 RP-1之间的相互作用显著降低了这种异常的T细胞活化，并导致T细胞数量减少。对治疗小鼠的CD 4（+）T细胞的体外分析显示，ICOS阻断显着降低了Th 1分化，而Th 2分化仅受到中度抑制。进一步的体外刺激实验表明，ICOS能够诱导小鼠CD 4（+）和CD 8（+）T细胞的增殖，但仅在IL-2存在的情况下。这些结果表明，ICOS不仅对T细胞效应子功能很重要，而且在CD 28信号传导存在下有助于T细胞应答的扩增阶段。
Both CD28 and ICOS are important costimulatory molecules that promote Ag-specific cellular and humoral immune reactions. Whereas CD28 is generally thought to be the most important molecule in the initiation of a T cell response, ICOS is considered to act during the effector phase. We have investigated the contribution of ICOS to T cell responses in the absence of CTLA-4-mediated inhibition. Mice lacking CTLA-4, which show spontaneous CD28-mediated CD4(+) T cell activation, expansion and differentiation, were treated with antagonistic alpha ICOS antibodies. Blocking the interaction between ICOS and its ligand B7RP-1 significantly reduced this aberrant T cell activation and caused a reduction in T cell numbers. In vitro analysis of CD4(+) T cells from treated mice revealed that ICOS blockade significantly reduced Th1 differentiation, while Th2 differentiation was only moderately inhibited. Further in vitro stimulation experiments demonstrated that ICOS is able to induce proliferation of murine CD4(+) and CD8(+) T cells but only in the presence of IL-2. These results indicate that ICOS is not only important for T cell effector function but also contributes to the expansion phase of a T cell response in the presence of CD28 signaling.