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Mapping the life histories of T cells

Nature Reviews Immunology volume 10, pages 621–631 (2010)Cite this article

Subjects

Key Points

  • To gain a more detailed understanding of T cell differentiation, methods are required with which the fate of T cells can be followed at the single-cell level.

  • Three different experimental strategies have been developed that can be used to follow cell fate at the single-cell level, namely continuous microscopy, single-cell adoptive transfer and cell marking with unique tags.

  • Single-cell transfer and cellular barcoding, in which individual naive CD8+ T cells are provided with unique genetic tags, have both been used to show that the progeny of single naive T cells can adopt multiple fates.

  • Cellular barcoding has also been used to demonstrate that the magnitude of antigen-specific CD8+ T cell responses following infection is primarily determined by clonal burst size.

  • To couple T cell functional states to subsequent cell-fate decisions, various gene expression reporter mice have been generated. The use of these mouse models has revealed that T cells with an effector phenotype can survive the contraction phase and enter the memory pool.

  • Understanding how prior signalling input regulates subsequent T cell behaviour will require the use of novel technologies that can monitor these signalling events. In many cases, the mapping of these receptor-mediated signals will require the engineering of synthetic signal transduction pathways.

Abstract

The behaviour of T cells is not fixed in the germ line, but is highly adaptable depending on experiences encountered during a T cell's life. To understand how different T cell subsets arise and how prior signalling input regulates subsequent T cell behaviour, approaches are required that couple a given T cell state to signals received by the cell, or by one of its ancestors, at earlier times. Here we describe recently developed technologies that have been used to determine the kinship of different T cell subsets and their prior functional characteristics. Furthermore, we discuss the potential value of new technologies that would allow assessment of T cell migration patterns and prior signalling events.

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Figure 1: Identifying kinship by comparing barcodes.
Figure 2: Measuring clonal diversity by counting barcodes.
Figure 3: Pitfalls of gene expression reporters in kinship analysis.
Figure 4: Tracking T cell migration by light-activated markers.
Figure 5: Strategies for revealing prior cell signalling.

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Acknowledgements

The authors thank S. Naik and G. Bendle for valuable input during conception of this manuscript and members of the Schumacher laboratory for stimulating discussions.

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  1. Division of Immunology, The Netherlands Cancer Institute, Amsterdam, 1066 CX, The Netherlands

    Ton N. M. Schumacher, Carmen Gerlach & Jeroen W. J. van Heijst

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  1. Ton N. M. Schumacher
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Glossary

Parabiotic mice

Pairs of mice that are surgically joined by cutaneous vascular anastomosis so that they have a common blood circulation while maintaining separate organs and tissues.

Intravital microscopy

Examination of biological processes by microscopy on living animals or viable explanted tissue.

β-selection

The process leading to the proliferation and survival of thymocytes that have successfully recombined the β-chain of the T cell receptor locus to express a functional pre-T cell receptor on their cell surface.

Cre–lox approach

A site-specific recombination system that is used to delete or rearrange genes by Cre recombinase activity. Two short DNA sequences (LoxP sites) are engineered to flank the target DNA. Depending on the orientation of the LoxP sites, expression of Cre recombinase leads to excision or inversion of the intervening sequence.

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Schumacher, T., Gerlach, C. & van Heijst, J. Mapping the life histories of T cells. Nat Rev Immunol 10, 621–631 (2010). https://doi.org/10.1038/nri2822

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