Borde Madhuri, Barrington Robert A, Heissmeyer Vigo, Carroll Michael C, Rao Anjana
The CBR Institute for Biomedical Research and the Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Immunol Rev. 2006 Apr;210:105-19. doi: 10.1111/j.0105-2896.2006.00370.x.
Signaling through lymphocyte antigen receptors has the potential to initiate several distinct outcomes: proliferation, differentiation, apoptosis, or functional unresponsiveness. Expansion and differentiation of effector T cells is required for defense against foreign antigens, whereas functional unresponsiveness, termed anergy, is a cell-intrinsic mechanism that contributes to peripheral self-tolerance. Other mechanisms of peripheral tolerance include the 'dominant' tolerance imposed by regulatory T cells and immunosuppression mediated by interleukin-10 and transforming growth factor-beta. T- and B-cell antigen receptor ligation induces an increase in intracellular calcium levels as well as activating additional signaling pathways that are further potentiated by costimulatory receptors. In this review, we argue that cell-intrinsic programs of peripheral anergy and tolerance are imposed by sustained calcium signaling in lymphocytes. We address in particular the role of the calcium-dependent transcription factor nuclear factor for activation of T cells, which is activated by antigen receptor stimulation and, depending on the presence or absence of input from its transcriptional partner, activator protein-1, dictates two distinct transcriptional programs: activation or tolerance.
增殖、分化、凋亡或功能无反应性。效应T细胞的扩增和分化对于抵御外来抗原是必需的，而功能无反应性，即无反应性，是一种细胞内在机制，有助于外周自身耐受。外周耐受的其他机制包括调节性T细胞施加的“显性”耐受以及白细胞介素-10和转化生长因子-β介导的免疫抑制。T细胞和B细胞抗原受体连接会导致细胞内钙水平升高，并激活其他信号通路，这些信号通路会被共刺激受体进一步增强。在这篇综述中，我们认为外周无反应性和耐受的细胞内在程序是由淋巴细胞中持续的钙信号传导所施加的。我们特别探讨了钙依赖性转录因子核因子活化T细胞的作用，它由抗原受体刺激激活，并根据其转录伙伴激活蛋白-1的输入情况，决定两种不同的转录程序：激活或耐受。
