Kawakami K, Parker D C
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worchester 01655.
Eur J Immunol. 1992 Jan;22(1):85-93. doi: 10.1002/eji.1830220114.
B cells get help in the antibody response by presenting antigen to helper T (Th) cells. Upon antigen recognition, T cells produce lymphokines that act as growth and differentiation factors for B cells, but resting B cells require additional helper signals that depend on cell contact with an activated Th cell. Like lymphokine secretion, contact help must be induced by antigen recognition or antigen receptor cross-linking in continuous Th cell lines. In the mouse, most CD4+ T cell lines can be classified into one of two stable differentiation states, Th1 or Th2, which produce different lymphokines and have different effector functions, activation requirements and cytoplasmic signalling mechanisms. This report demonstrates additional differences between Th1 and Th2 cell lines in the signalling pathways leading from the T cell antigen receptor to the induction of Th functions. In a system dependent on antigen presentation by B cells, B cell proliferation driven by Th2 cells but not Th1 cells was blocked by acute treatment with phorbol esters. Further experiments showed that phorbol esters blocked the induction of both contact help and lymphokine production in Th2 cells but not in Th1 cells. However, depletion of protein kinase C (PKC) activity by prolonged treatment of T cells with high concentrations of phorbol esters blocked induction of contact help and lymphokine production in Th1 cells but not in Th2 cells. These findings support the hypothesis that Th2 cells use a signalling pathway that is independent of PKC and that PKC activation can block this pathway. Since contact help and lymphokine secretion are affected in parallel, this difference between Th1 and Th2 cells probably reflects early events in the signalling pathway. Contact help and lymphokine production could be dissociated with cholera toxin and other cAMP agonists, but this dissociation could be explained by non-cAMP-related effects of cholera toxin on induction of contact help in Th2 cells, and by the direct effect of cAMP agonists on interleukin 2 gene transcription in Th1 cells reported by other laboratories.
B细胞通过将抗原呈递给辅助性T（Th）细胞来获得抗体应答中的帮助。在识别抗原后，T细胞产生淋巴因子，这些淋巴因子作为B细胞的生长和分化因子，但静止的B细胞需要额外的辅助信号，这些信号依赖于与活化的Th细胞的细胞接触。与淋巴因子分泌一样，接触性帮助必须由连续Th细胞系中的抗原识别或抗原受体交联诱导。在小鼠中，大多数CD4 + T细胞系可分为两种稳定的分化状态之一，即Th1或Th2，它们产生不同的淋巴因子，具有不同的效应功能、激活要求和细胞质信号传导机制。本报告证明了Th1和Th2细胞系在从T细胞抗原受体到Th功能诱导的信号通路中存在其他差异。在一个依赖于B细胞呈递抗原的系统中，由Th2细胞而非Th1细胞驱动的B细胞增殖被佛波酯急性处理所阻断。进一步的实验表明，佛波酯阻断了Th2细胞中接触性帮助和淋巴因子产生的诱导，但未阻断Th1细胞中的诱导。然而，用高浓度佛波酯长时间处理T细胞耗尽蛋白激酶C（PKC）活性，阻断了Th1细胞中接触性帮助和淋巴因子产生的诱导，但未阻断Th2细胞中的诱导。这些发现支持了这样的假设，即Th2细胞使用一条独立于PKC的信号通路，并且PKC激活可以阻断该通路。由于接触性帮助和淋巴因子分泌受到平行影响，Th1和Th2细胞之间的这种差异可能反映了信号通路中的早期事件。接触性帮助和淋巴因子产生可以用霍乱毒素和其他cAMP激动剂解离，但这种解离可以通过霍乱毒素对Th2细胞中接触性帮助诱导的非cAMP相关效应，以及其他实验室报道的cAMP激动剂对Th1细胞中白细胞介素2基因转录的直接效应来解释。
