Neuroinflammation Unit, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen Biocentre, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
J Mol Cell Biol. 2012 Apr;4(2):70-8. doi: 10.1093/jmcb/mjr035. Epub 2011 Dec 13.
Complex immune responses have evolved to protect multicellular organisms against the invasion of pathogens. This has exerted strong developmental pressure for specialized functions that can also limit damage to self-tissue. Two arms of immunity, the innate and adaptive immune systems, have evolved for quick, non-specific immune responses to pathogens and more efficient, long-lasting ones upon specific recognition of recurrent pathogens. Specialized cells have arisen as the sentinels of these functions, including macrophages, natural killer (NK), and T and B-lymphocytes. Interestingly, a population of immune cells that can exert both of these complex functions, NKT cells, not only share common functions but also exhibit shared cell surface markers of cells of both arms of the immune system. These features, in combination with sophisticated maintenance of immune homeostasis, will be discussed. The recent finding of self-peptide reactivity of NKT cells in the context of CD1d, with capacity to regulate multiple autoimmune and inflammatory conditions, motivates the current proposal that self-reactive NKT cells might be the ancestral link between present NK and T cells. Their parallel selection through evolution by higher vertebrates could be related to their central function as master regulators of immune homeostasis that in part is shared with regulatory T cells. Hypothetical views on how self-reactive NKT cells secure such a central role will also be proposed.
复杂的免疫反应已经进化到可以保护多细胞生物免受病原体的侵害。这为专门的功能施加了强大的发展压力，这些功能也可以限制对自身组织的损伤。免疫系统的两个分支，先天免疫系统和适应性免疫系统，已经进化出了快速、非特异性的免疫反应来对抗病原体，以及在特异性识别反复出现的病原体时更有效、更持久的免疫反应。专门的细胞已经出现，作为这些功能的哨兵，包括巨噬细胞、自然杀伤 (NK) 细胞和 T 和 B 淋巴细胞。有趣的是，一群既能发挥这两种复杂功能的免疫细胞，即 NKT 细胞，不仅具有共同的功能，而且还表现出免疫细胞两个分支的细胞表面标记物的共同特征。这些特征，结合复杂的免疫稳态维持，将被讨论。最近发现 NKT 细胞在 CD1d 背景下对自身肽的反应性，具有调节多种自身免疫和炎症性疾病的能力，这促使人们提出当前的假设，即自身反应性 NKT 细胞可能是 NK 和 T 细胞之间现存的祖先联系。高等脊椎动物通过进化平行选择它们可能与它们作为免疫稳态主要调节者的核心功能有关，部分功能与调节性 T 细胞共享。关于自身反应性 NKT 细胞如何确保这种核心作用的假设观点也将被提出。
