Freud Aharon G, Caligiuri Michael A
Medical Scientist Program, The Ohio State University, Columbus, OH 43210, USA.
Immunol Rev. 2006 Dec;214:56-72. doi: 10.1111/j.1600-065X.2006.00451.x.
Our understanding of human natural killer (NK) cell development lags far behind that of human B- or T-cell development. Much of our recent knowledge of this incomplete picture comes from experimental animal models that have aided in identifying fundamental in vivo processes, including those controlling NK cell homeostasis, self-tolerance, and the generation of a diverse NK cell repertoire. However, it has been difficult to fully understand the mechanistic details of NK cell development in humans, primarily because the in vivo cellular intermediates and microenvironments of this developmental pathway have remained elusive. Although there is general consensus that NK cell development occurs primarily within the bone marrow (BM), recent data implicate secondary lymphoid tissues as principal sites of NK cell development in humans. The strongest evidence stems from the observation that the newly described stages of human NK cell development are naturally and selectively enriched within lymph nodes and tonsils compared with blood and BM. In the current review, we provide an overview of these recent findings and discuss these in the context of existing tenets in the field of lymphocyte development.
我们对人类自然杀伤（NK）细胞发育的了解远远落后于对人类B细胞或T细胞发育的了解。我们对这一尚不完整图景的最新认识，很大程度上来自实验动物模型，这些模型有助于确定体内的基本过程，包括那些控制NK细胞稳态、自身耐受性以及多样化NK细胞库生成的过程。然而，要全面了解人类NK细胞发育的机制细节一直很困难，主要原因是该发育途径的体内细胞中间体和微环境仍然难以捉摸。尽管人们普遍认为NK细胞发育主要发生在骨髓（BM）内，但最近的数据表明，二级淋巴组织是人类NK细胞发育的主要部位。最有力的证据来自以下观察结果：与血液和骨髓相比，新描述的人类NK细胞发育阶段在淋巴结和扁桃体中自然且选择性地富集。在本综述中，我们概述了这些最新发现，并在淋巴细胞发育领域现有原则的背景下对其进行讨论。
