Gelfand E W, Mills G B, Cheung R K, Lee J W, Grinstein S
Immunol Rev. 1987 Feb;95:59-87. doi: 10.1111/j.1600-065x.1987.tb00500.x.
The importance of increases in [Ca2+]i, stimulation of Na+/H+ exchange, and turnover of membrane phospholipids as signals for mitogen-induced activation of human T cells has been reviewed. In the presence of optimal concentrations of lectin and appropriately presented antigen, T cells increase [Ca2+]i, secrete IL2, express IL2 receptors and later divide. An increase in [Ca2+]i is critical for IL2 secretion in contrast to the requirements for IL2 receptor expression and IL2-IL2 receptor interaction. Treatment of T cells with TPA appears to bypass the requirement for an increase in [Ca2+]i for IL2 secretion and cell proliferation, indicating that various mitogens can trigger T cells through both [Ca2+]i-dependent and [Ca2+]i-independent pathways. Influx of Ca2+ from the extracellular milieu appears essential for the induced increase in [Ca2+]i associated with IL2 secretion. These increases in [Ca2+]i, which are correlated with the degree of lymphoproliferation and IL2 secretion, are sensitive to changes in membrane potential. The changes in [Ca2+]i are not mediated by the opening of voltage-gated K+ channels but the nature of the potential-sensitive event remains to be determined. The membrane potential effects may be mediated through the gating of a putative Ca2+ channel or by affecting the inward electrochemical Ca2+ gradient. It is clear that lymphoid cells of both T and B lineage possess a functional Na+/H+ antiport, which plays a central role in the regulation of pHi. It is also generally agreed that the antiport can be stimulated by mitogens, co-mitogens and by agents that induce differentiation. The meaning of this stimulation is not, however, entirely understood. It may be an essential signal or link in the series of events triggered by the binding of ligands to their membrane receptors. Alternatively, it may represent an ancillary event, intended to increase H+ ejection in anticipation of an increased metabolic rate. Finally, a third possible reason for the stimulation of Na+/H+ exchange could be to increase the osmotic content of the cells, inducing cell swelling that may be an early requirement for cellular growth. Indeed, amiloride-sensitive cellular swelling has been detected electronically following treatment of T lymphocytes with TPA (Grinstein et al. 1985a). PHA is a potent activator of phosphatidylinositol hydrolysis. In other cell types, receptors are coupled to phospholipase C by a G protein(s). However, the transducing mechanism in human peripheral blood lymphocytes does not appear to be a pertussis toxin-sensitive G protein(s).(ABSTRACT TRUNCATED AT 400 WORDS)
已有综述阐述了细胞内钙离子浓度（[Ca2+]i）升高、钠氢交换（Na+/H+ exchange）的刺激以及膜磷脂周转作为丝裂原诱导人T细胞活化信号的重要性。在存在最佳浓度的凝集素和适当呈递的抗原时，T细胞会升高[Ca2+]i、分泌白细胞介素2（IL2）、表达IL2受体并随后分裂。与IL2受体表达和IL2 - IL2受体相互作用的需求相比，[Ca2+]i升高对于IL2分泌至关重要。用佛波酯（TPA）处理T细胞似乎绕过了IL2分泌和细胞增殖对[Ca2+]i升高的需求，这表明各种丝裂原可通过依赖[Ca2+]i和不依赖[Ca2+]i的途径触发T细胞。细胞外环境中Ca2+的内流似乎是诱导与IL2分泌相关的[Ca2+]i升高所必需的。这些与淋巴细胞增殖程度和IL2分泌相关的[Ca2+]i升高对膜电位变化敏感。[Ca2+]i的变化不是由电压门控钾通道的开放介导的，但电位敏感事件的性质仍有待确定。膜电位效应可能是通过假定的Ca2+通道的门控介导的，或者是通过影响内向电化学Ca2+梯度介导的。显然，T和B淋巴细胞系的淋巴细胞都具有功能性的钠氢反向转运体，其在细胞内pH值（pHi）调节中起核心作用。人们也普遍认为，该反向转运体可被丝裂原、共刺激原和诱导分化的试剂刺激。然而，这种刺激的意义尚未完全理解。它可能是配体与其膜受体结合触发的一系列事件中的一个基本信号或环节。或者，它可能代表一个辅助事件，旨在预期代谢率增加时增加H+排出。最后，刺激钠氢交换的第三个可能原因可能是增加细胞的渗透压含量，诱导细胞肿胀，这可能是细胞生长的早期需求。事实上，在用TPA处理T淋巴细胞后，已通过电子检测到amiloride敏感的细胞肿胀（格林斯坦等人，1985a）。植物血凝素（PHA）是磷脂酰肌醇水解的有效激活剂。在其他细胞类型中，受体通过一种或多种G蛋白与磷脂酶C偶联。然而，人外周血淋巴细胞中的转导机制似乎不是对百日咳毒素敏感的一种或多种G蛋白。（摘要截短于400字）
