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Annu Rev Immunol. 2016 May 20;34:65-92. doi: 10.1146/annurev-immunol-032414-112014. Epub 2015 Dec 11.

T Cell Fate at the Single-Cell Level.

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Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 München, Germany; email: ,
Division of Immunology, The Netherlands Cancer Institute (NKI), 1066 CX Amsterdam, The Netherlands; email:


T cell responses display two key characteristics. First, a small population of epitope-specific naive T cells expands by several orders of magnitude. Second, the T cells within this proliferating population take on diverse functional and phenotypic properties that determine their ability to exert effector functions and contribute to T cell memory. Recent technological advances in lineage tracing allow us for the first time to study these processes in vivo at single-cell resolution. Here, we summarize resulting data demonstrating that although epitope-specific T cell responses are reproducibly similar at the population level, expansion potential and diversification patterns of the offspring derived from individual T cells are highly variable during both primary and recall immune responses. In spite of this stochastic response variation, individual memory T cells can serve as adult stem cells that provide robust regeneration of an epitope-specific tissue through population averaging. We discuss the relevance of these findings for T cell memory formation and clinical immunotherapy.


T cell differentiation; T cell memory; immunotherapy; robustness; stemness; stochasticity

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