Cutting edge:: Distinct motifs within CD28 regulate T cell proliferation and induction of Bcl-XL
Cutting edge:: Distinct motifs within CD28 regulate T cell proliferation and induction of Bcl-XL
复制标题
DOI：
10.4049/jimmunol.166.9.5331
复制
发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Green, JM
中科院分区：
文献类型：
--
作者：
Burr, JS;Savage, NDL;Green, JM
CD 28在T细胞活化中提供重要的共刺激信号，其调节包括增殖和存活在内的多个细胞过程。几种信号转导途径被CD 28激活;然而，CD 28调节T细胞功能的确切生化机制仍然存在争议。将逆转录病毒基因转移到来自TCR转基因、CD 28缺陷型小鼠的原代T细胞中，用于确定CD 28内决定功能的特异性序列。CD 28胞浆区的离散区域被鉴定为差异调节T细胞增殖和抗凋亡蛋白Bcl-X-L的诱导。C-末端脯氨酸残基的突变废除了CD 28共刺激的增殖和细胞因子调节特征，同时保留Bcl-X-L诱导。相反，磷脂酰肌醇3-激酶激活的重要残基的突变部分抑制增殖，但阻止诱导Bcl-X-L。因此，CD 28调节Bcl-X-L增殖和诱导的能力映射到不同的基序，表明独立的信号级联调节这些生物学效应。
CD28 provides an important costimulatory signal in T cell activation that regulates multiple cellular processes including proliferation and survival. Several signal transduction pathways are activated by CD28; however, the precise biochemical mechanism by which CD28 regulates T cell function remains controversial. Retroviral gene transfer into primary T cells from TCR-transgenic, CD28-deficient mice was used to determine the specific sequences within CD28 that determine function. Discrete regions of the cytoplasmic domain of CD28 were identified that differentially regulate T cell proliferation and induction of the anti-apoptotic protein Bcl-X-L, Mutation of C-terminal proline residues abrogated the proliferative and cytokine regulatory features of CD28 costimulation while preserving Bcl-X-L induction. Conversely, mutation of residues important in phosphatidylinositol 3-kinase activation partially inhibited proliferation but prevented induction of Bcl-X-L. Thus the ability of CD28 to regulate proliferation and induction of Bcl-X-L map to distinct motifs, suggesting independent signaling cascades modulate these biologic effects.