Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, Firenze, 50134, Italy.
Cytometry A. 2014 Jan;85(1):36-42. doi: 10.1002/cyto.a.22348. Epub 2013 Sep 5.
CD4+ T cells can be subdivided from a functional point of view into two main subsets: effector cells, which provide protection against exogenous offending agents, and regulatory T (Treg) cells whose function is to avoid autoimmune reactions and to stop the effector response against exogenous antigens, when the response itself becomes dangerous for the host. Human effector CD4+ T lymphocytes can be additionally classified into lineages based mainly on their immunological functions that are supported by distinct profile of cytokine, transcription factor, and homing receptors expression. In the last years, beyond the well known populations of human T helper (Th) lymphocytes, Th1 and Th2 cells, other populations have been discovered and phenotypically characterized. These include the Th17 subset, which is certainly the most intensively studied, but also Th22, Th9, and T follicular helper (Tfh) lymphocytes. In addition to their protective functions, these T helper populations are also involved in the pathogenesis of several inflammatory immune-mediated disorders. Th1 and Th17 cells are involved in the pathogenesis of organ-specific autoimmune diseases and other chronic inflammatory disorders, whereas allergen-specific Th2 lymphocytes play a crucial role in allergy. Although classically viewed as distinct lineages, recent evidence indicate that CD4+ T cells, particularly the Th17 subset, are more plastic than previously thought. It is not fully understood how often such plasticity occurs in the course of physiologic responses to pathogens and what its importance is in protective immunity, but in inflammatory conditions Th17 lymphocytes that have shifted towards a Th1 or Th2 phenotype, acquiring the ability to produce IFN-γ or IL-4, and seem to be particularly aggressive and more pathogenic than the unshifted cells. In this context, the possibility to interfere with this modulation of phenotype can be considered a possible target for developing novel therapeutic strategies in the above mentioned diseases.
CD4+ T 细胞从功能角度可以分为两个主要亚群：效应细胞，提供针对外源性致病因子的保护；调节性 T（Treg）细胞，其功能是避免自身免疫反应，并在针对外源性抗原的效应反应变得对宿主有危险时停止该反应。人类效应 CD4+ T 淋巴细胞还可以根据其免疫功能进一步分为不同谱系，这些功能由不同的细胞因子、转录因子和归巢受体表达谱支持。近年来，除了众所周知的人类辅助性 T（Th）淋巴细胞 Th1 和 Th2 细胞外，还发现并表型鉴定了其他群体。这些群体包括 Th17 亚群，这是研究最多的群体，但也包括 Th22、Th9 和滤泡辅助性 T（Tfh）淋巴细胞。除了其保护功能外，这些辅助性 T 细胞群体还参与了几种炎症性免疫介导疾病的发病机制。Th1 和 Th17 细胞参与器官特异性自身免疫性疾病和其他慢性炎症性疾病的发病机制，而过敏原特异性 Th2 淋巴细胞在过敏中起着至关重要的作用。尽管经典上被视为不同的谱系，但最近的证据表明，CD4+ T 细胞，特别是 Th17 亚群，比以前认为的更具可塑性。尚不完全清楚这种可塑性在针对病原体的生理反应过程中发生的频率及其在保护性免疫中的重要性，但在炎症条件下，已经向 Th1 或 Th2 表型转变的 Th17 淋巴细胞获得了产生 IFN-γ 或 IL-4 的能力，并且似乎比未转变的细胞更具侵袭性和致病性。在这种情况下，可以考虑干扰这种表型调节作为开发上述疾病新型治疗策略的可能目标。
