Romagnani S
Center of Excellence for Research, Transfer, and High Education DENOTHE, University of Florence, Florence, Italy.
Clin Exp Allergy. 2006 Nov;36(11):1357-66. doi: 10.1111/j.1365-2222.2006.02606.x.
The T cell branch of the immune system can respond to a virtually infinite variety of exogenous antigens, thus including the possibility of self-antigen recognition and dangerous autoimmune reactions. Therefore, regulatory mechanisms operate both during ontogeny within the thymus and after birth in the periphery. The control of self-reactive T cells occurs through a process of negative selection that results in apoptosis of T cells showing high affinity for self-peptides expressed at the thymic level by means of promiscuous gene expression. Self-reactive T cells escaped to negative selection are controlled in the periphery by other regulatory mechanisms, the most important being natural Foxp3+ T regulatory (Treg) cells. Regulation is also required to control excessive effector T cell responses against exogenous antigens, when they become dangerous for the body. Three types of effector T cells have been recognized: T helper 1 (Th1) cells, which are protective against intracellular bacteria; Th2 cells, which play some role in the protection against nematodes, but are responsible for allergic reactions; Th17 cells, which are probably effective in the protection against extracellular bacteria, but also play a role in the amplification of autoimmune disorders. Abnormal or excessive Th effector responses are regulated by different mechanisms. Redirection or immune deviation of Th1- or Th2-dominated responses is provided by cytokines [interferon-gamma (IFN-gamma) vs. interleukin-4 (IL-4)] produced by the same cell types and by the CXCR3-binding chemokines CXCL4 and CXCL10. Moreover, both Th1 and Th2 responses can be suppressed by adaptive Treg cells through contact-dependent mechanisms and/or the production of IL-10 and transforming growth factor-beta (TGF-beta). Finally, TGF-beta1 can promote the development of both Th17 effector and adaptive Treg cells, while the contemporaneous production of IL-6 contributes to the development of Th17 cells, but inhibits Treg cells. The development of Th17 cells is also down-regulated by IL-4 produced by Th2 cells and by IFN-gamma produced by Th1 cells.
免疫系统的T细胞分支能够对几乎无限多样的外源性抗原作出反应，因此存在识别自身抗原和引发危险自身免疫反应的可能性。所以，调控机制在胸腺内的个体发育过程中以及出生后的外周组织中均发挥作用。对自身反应性T细胞的控制通过阴性选择过程实现，该过程导致对通过混杂基因表达在胸腺水平表达的自身肽具有高亲和力的T细胞发生凋亡。逃避阴性选择的自身反应性T细胞在外周组织中由其他调控机制控制，其中最重要的是天然Foxp3 + T调节（Treg）细胞。当针对外源性抗原的效应T细胞反应对身体造成危险时，也需要进行调控以控制过度的反应。已识别出三种类型的效应T细胞：辅助性T细胞1（Th1），可抵御细胞内细菌；Th2细胞，在抵御线虫方面发挥一定作用，但会引发过敏反应；Th17细胞，可能在抵御细胞外细菌方面有效，但也在自身免疫性疾病的放大过程中起作用。异常或过度的Th效应反应由不同机制调控。由相同细胞类型产生的细胞因子[干扰素 - γ（IFN - γ）与白细胞介素 - 4（IL - 4）]以及与CXCR3结合的趋化因子CXCL4和CXCL10可实现Th1或Th2主导反应的重定向或免疫偏离。此外，适应性Treg细胞可通过接触依赖性机制和/或产生IL - 10和转化生长因子 - β（TGF - β）来抑制Th1和Th2反应。最后，TGF - β1可促进Th17效应细胞和适应性Treg细胞的发育，而IL - 6的同时产生有助于Th17细胞的发育，但会抑制Treg细胞。Th2细胞产生的IL - 4和Th1细胞产生的IFN - γ也会下调Th17细胞的发育。
