Correa M R, Ochoa A C, Ghosh P, Mizoguchi H, Harvey L, Longo D L
Biomira USA, Inc., Cranbury, NJ 08512, USA.
J Immunol. 1997 Jun 1;158(11):5292-6.
The TCR alpha beta or -gamma delta chains bind the peptide ligand, whereas the associated CD3 delta epsilon gamma and TCR zeta subunits couple the TCR to intracellular signal transduction components. Recently, several groups have described marked alterations in signal transduction elements in T cells from cancer patients or in mice bearing tumor for a few weeks (>26 days). The sequence in which these alterations develop is unknown. The aim of this study was to explore the kinetics of the development of alterations in signal transduction molecules (TCR zeta chain, NF kappaB family proteins, and tyrosine kinase p56(lck)) in mice bearing MC38 colon adenocarcinoma. The results demonstrate that alterations in NF kappaB family proteins, specifically the failure of p65 translocation to the nucleus, occur earlier and more frequently than the decrease in zeta-chain. These defects are paralleled by an impaired ability to produce Th1 cytokines (IL-2 and IFN-gamma). These initial changes are followed by the eventual loss of TCR zeta chain and p56(lck) and a marked decrease in cytotoxic function. An increased rate of lysosomal degradation is one of the mechanisms responsible for the loss of zeta-chain.
TCRαβ或γδ链结合肽配体，而相关的CD3δεγ和TCRζ亚基将TCR与细胞内信号转导成分偶联。最近，几个研究小组描述了癌症患者T细胞或携带肿瘤数周（>26天）的小鼠T细胞中信号转导元件的显著改变。这些改变发生的顺序尚不清楚。本研究的目的是探讨MC38结肠腺癌荷瘤小鼠中信号转导分子（TCRζ链、NF-κB家族蛋白和酪氨酸激酶p56^（lck））改变的发展动力学。结果表明，NF-κB家族蛋白的改变，特别是p65向细胞核转位的失败，比ζ链的减少更早且更频繁地发生。这些缺陷伴随着产生Th1细胞因子（IL-2和IFN-γ）的能力受损。这些初始变化随后是TCRζ链和p56^（lck）的最终丧失以及细胞毒性功能的显著降低。溶酶体降解速率增加是ζ链丧失的机制之一。
