Ramanathan Sheela, Gagnon Julien, Ilangumaran Subburaj
Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
Arch Immunol Ther Exp (Warsz). 2008 Sep-Oct;56(5):311-23. doi: 10.1007/s00005-008-0033-2.
Development of T lymphocytes and their survival in the periphery are dependent on signals emanating from cytokine receptors as well as the T cell antigen receptor (TCR). These two signaling pathways play distinct and complementary roles at various stages of T cell development, maturation, survival, activation and differentiation. During immune response to foreign antigens initiated by TCR signaling, cytokines play a key role in the expansion of activated T cells. Even though the initial activation of T cells occurs via the TCR, this requirement can be overcome under certain circumstances. During lymphopenia, cytokines trigger memory CD8(+) T cells to undergo antigen non-specific homeostatic expansion, whereas naïve CD8(+) T cells require both cytokines and TCR signaling. Recent reports show certain combinations of cytokines can induce proliferation and effector functions of naïve CD8(+) T cells without concomitant stimulation via the TCR. While such antigen non-specific stimulation of naïve T cells might significantly boost the adaptive immune response, it could also have an undesirable effect of triggering potentially autoreactive cells. Understanding the mechanisms and the regulation of cytokine-driven stimulation of naïve CD8(+) T cells may lead to novel strategies of intervention for autoimmune diseases. On the other hand, in vitro expansion of naïve CD8(+) T cells by certain combinations of cytokines could be used to generate tumor-specific cells with ideal properties for cellular immunotherapy of cancer.
T淋巴细胞的发育及其在外周的存活依赖于细胞因子受体以及T细胞抗原受体（TCR）发出的信号。这两条信号通路在T细胞发育、成熟、存活、激活和分化的各个阶段发挥着不同但互补的作用。在由TCR信号引发的对外来抗原的免疫反应过程中，细胞因子在活化T细胞的扩增中起关键作用。尽管T细胞的初始激活是通过TCR发生的，但在某些情况下这一要求可以被克服。在淋巴细胞减少期间，细胞因子触发记忆性CD8(+) T细胞进行抗原非特异性的稳态扩增，而初始CD8(+) T细胞则需要细胞因子和TCR信号两者。最近的报告显示，某些细胞因子组合可以诱导初始CD8(+) T细胞增殖并发挥效应功能，而无需通过TCR同时进行刺激。虽然这种对初始T细胞的抗原非特异性刺激可能会显著增强适应性免疫反应，但它也可能产生触发潜在自身反应性细胞的不良影响。了解细胞因子驱动的初始CD8(+) T细胞刺激的机制和调控可能会带来针对自身免疫性疾病的新型干预策略。另一方面，通过某些细胞因子组合在体外扩增初始CD8(+) T细胞可用于生成具有理想特性的肿瘤特异性细胞，用于癌症的细胞免疫治疗。
