Resting and activated T cells display different requirements for CD8 molecules.
Resting and activated T cells display different requirements for CD8 molecules.
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DOI：
10.1084/jem.179.6.2005
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发表时间：
1994-06-01
期刊：
影响因子：
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通讯作者：
Sprent J
中科院分区：
文献类型：
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作者：
Cai Z;Sprent J
使用来自2C T细胞受体（TCR）转基因小鼠的克隆型阳性（1B 2+）T细胞来确定CD 8分子在对I类同种异体抗原的初次应答的诱导期与效应期中的作用。报告了三项主要调查结果。首先，在外源性淋巴因子的存在下，静息的CD 8 + 2C细胞对两种同种异体抗原Ld和Kbm 11产生了强烈的增殖反应。然而，在没有添加淋巴因子的情况下，CD 8 + 2C细胞仅对Ld有反应，而对Kbm 11没有反应; Ld刺激白细胞介素2（IL-2）和IL-2受体（R）的合成，而Kbm 11仅引起IL-2 R的合成。因此，CD 8 + 2C细胞的主要应答对Ld是辅助细胞非依赖性的（HI），但对Kbm 11是辅助细胞依赖性的（HD），推测反映了Ld是比Kbm 11更强的抗原。其次，与CD 8+细胞相反，CD 8 - 2C细胞对强Ld抗原仅产生HD而非HI应答;相反，选择CD 8hi细胞的小亚群使2C细胞对弱Kbm 11抗原产生HI应答。这些发现，以及杂合与纯合刺激细胞的实验表明，HI和HD反应反映了T抗原呈递细胞（APC）相互作用的总体亲和力的差异：高亲和力相互作用导致强细胞内信号传导和HI反应，而低亲和力相互作用导致弱信号传导和HD反应;高亲和力T/APC相互作用严重依赖于CD 8表达。第三，发现CD 8表达对于CTL活性的重要性低于对于原发性增殖反应的重要性。因此，与HI增殖反应相反，2C细胞对Ld的CTL反应是CD 8非依赖性的。然而，在存在有限剂量的抗TCR（1B 2）抗体的情况下，Ld靶标的2C裂解变得强烈依赖于CD 8。总的来说，这些数据表明，对于T细胞诱导和效应子功能的表达，CD 8分子通过促进TCR与抗原接触或将激酶（p56 lck）递送至TCR/CD 3复合物或两者，在增强TCR介导的信号传导中起决定性作用。
Clonotype-positive (1B2+) T cells from 2C T cell receptor (TCR) transgenic mice were used to define the role of CD8 molecules in the induction phase vs. the effector phase of the primary response to class I alloantigens. Three main findings are reported. First, in the presence of exogenous lymphokines, resting CD8+ 2C cells gave strong proliferative responses to two alloantigens, Ld and Kbm11. In the absence of added lymphokines, however, CD8+ 2C cells responded only to Ld and not to Kbm11; Ld stimulated both interleukin 2 (IL-2) and IL-2 receptor (R) synthesis, whereas Kbm11 elicited only IL-2R synthesis. The primary response of CD8+ 2C cells was thus helper-independent (HI) to Ld but helper-dependent (HD) to Kbm11, presumably reflecting that Ld is a stronger antigen than Kbm11. Second, in contrast to CD8+ cells, CD8- 2C cells mounted only an HD and not an HI response to the strong Ld antigen; conversely, selecting for a minor subset of CD8hi cells enabled 2C cells to mount an HI response to the weak Kbm11 antigen. These findings, together with experiments with heterozygous vs. homozygous stimulator cells, suggest that HI and HD responses reflect differences in the overall avidity of T antigen presenting cell (APC) interaction: high-avidity interaction leads to strong intracellular signaling and an HI response, whereas low-avidity interaction causes weak signaling and an HD response; high-avidity T/APC interaction is heavily dependent on CD8 expression. Third, CD8 expression was found to be less important for CTL activity than for primary proliferative responses. Thus, in contrast to HI proliferative responses, CTL responses of 2C cells to Ld were CD8 independent. However, 2C lysis of Ld targets became strongly CD8 dependent in the presence of limiting doses of anti-TCR (1B2) antibody. Collectively, the data suggest that, both for T cell induction and the expression of effector function, CD8 molecules play a decisive role in augmenting TCR-mediated signaling, either by promoting TCR contact with antigen or delivering kinases (p56lck) to the TCR/CD3 complex, or both.