CD28 costimulation prevents cell death during primary T cell activation.
CD28 costimulation prevents cell death during primary T cell activation.
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DOI：
10.4049/jimmunol.157.2.636
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发表时间：
1996-07
影响因子：
4.4
通讯作者：
P. Noel;L. Boise;J. Green;Craig B. Thompson
中科院分区：
文献类型：
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作者：
P. Noel;L. Boise;J. Green;Craig B. Thompson
CD 28已被证明在增强T细胞增殖和效应子功能中起重要作用。还报道了通过CD 28的共刺激增强人T细胞存活。在本报告中，我们通过比较野生型和CD 28缺陷小鼠T细胞的存活特性，进一步研究了CD 28在调节T细胞存活中的作用。CD 28共刺激抗CD 3激活的细胞增强了野生型T细胞的活力，但对CD 28缺陷小鼠没有影响。CTLA 4 Ig处理将野生型T细胞活力降低至与CD 28缺陷型T细胞相当的水平。CD 28在T细胞活化过程中增强存活的能力与其上调细胞存活基因bcl-xL的蛋白产物的能力呈正相关。在野生型和CD 28缺陷型T细胞之间没有观察到Bcl-2或Fas的表达差异。在体外活化过程中的CD 28依赖性增强细胞存活被认为是独立的Fas表达，作为CD 28共刺激增强T细胞的存活，在野生型和lpr动物的可比水平。CD 28缺陷动物和CTLA 4 Ig处理的野生型动物的细胞死亡显示出凋亡的形态学特征。此外，ICE蛋白酶的抑制剂可以逆转在不存在CD 28共刺激的情况下由TCR接合诱导的细胞死亡。因此，CD 28共刺激不仅增强了通过TCR活化的细胞的增殖扩增，而且增加了单个细胞在T细胞活化期间存活的可能性。
CD28 has been demonstrated to play an important role in augmenting T cell proliferation and effector function. Costimulation through CD28 has also been reported to enhance human T cell survival. in this report, we have further investigated the role of CD28 in regulating T cell survival by comparing the survival characteristics of T cells from wild-type and CD28-deficient mice. CD28 costimulation of anti-CD3-activated cells augmented the viability of T cells from wild-type but not from CD28-deficient mice. CTLA4Ig treatment reduced wild-type T cell viability to a level comparable with CD28-deficient T cells. The ability of CD28 to enhance survival during T cell activation correlated positively with its ability to up-regulate the protein product of the cell survival gene bcl-xL. No differences in the expression of either Bcl-2 or Fas were observed between wild-type and CD28-deficient T cells. The CD28-dependent enhancement of cell survival during in vitro activation was found to be independent of Fas expression, as CD28 costimulation enhanced T cell survival to comparable levels in both wild-type and lpr animals. Cell death in CD28-deficient animals and in wild-type animals treated with CTLA4Ig displayed the morphologic characteristics of apoptosis. Additionally, inhibitors of ICE proteases could reverse cell death induced by TCR engagement in the absence of CD28 costimulation. Thus, CD28 costimulation not only enhances the proliferative expansion of cells activated through the TCR but also increases the likelihood that individual cells survive during T cell activation.