Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg, Freiburg, Germany.
Department of Microbiology & Immunobiology, Harvard Medical School, Boston, MA, USA.
Trends Immunol. 2014 Apr;35(4):170-7. doi: 10.1016/j.it.2014.02.006. Epub 2014 Mar 20.
Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various subsets. A long-standing question in the field has been how this cellular diversification is achieved. Conceptually, diverse cellular output may either arise from every single cell or only from populations of naïve cells. Furthermore, such diversity may either be driven by cell-intrinsic heterogeneity or by external, niche-derived signals. In this review, we discuss how recently developed technologies have allowed the analysis of the mechanisms underlying T cell diversification at the single cell level. In addition, we outline the implications of this work on our understanding of the formation of immunological memory, and describe a number of unresolved key questions in this field.
初次感染时，识别自身同源抗原的幼稚 T 细胞被激活、增殖，并同时分化为各种亚群。该领域长期存在的一个问题是，这种细胞多样化是如何实现的。从概念上讲，多样化的细胞输出可能来自于每个单独的细胞，也可能仅来自于幼稚细胞群体。此外，这种多样性可能是由细胞内在的异质性驱动的，也可能是由外部小生境衍生的信号驱动的。在这篇综述中，我们讨论了最近开发的技术如何允许在单细胞水平上分析 T 细胞多样化的机制。此外，我们概述了这项工作对我们理解免疫记忆形成的意义，并描述了该领域一些未解决的关键问题。
