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Thymic microenvironments for T cell differentiation and selection

Abstract

The adult thymus provides a variety of specialized microenvironments that support and direct T cell differentiation and selection. In this review, we summarize recent advances in the understanding of the function of microenvironments in shaping a diverse T cell repertoire. In particular, we focus on how thymocytes move in and out of these specialized thymic compartments in response to homing signals, differential chemokine gradients and other factors that regulate T cell migration. In addition, we discuss the diverse developmental signals provided by these microenvironments that contribute to the generation of divergent T cell lineages.

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Acknowledgements

We thank M. Anderson (University of California at San Francisco), P. Bousso (Pasteur Institute), H. Petrie (Scripps Florida) and C. Witt (University of Texas at San Antonio) for comments on the manuscript. Supported by the Human Frontier Science Program (T.C.) and the National Institutes of Health (AI32985 and AI053030 to E.A.R.).

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Competing interests

The authors declare no competing financial interests.

Correspondence to Ellen A Robey.

Supplementary information

  1. Supplementary Video 1

    Slow, meandering migration of cortical thymocytes expressing diverse TCRs. Real-time imaging of GFP+ thymocytes in the cortex of intact thymic lobes. Green represents the fluorescent signal from GFP thymocytes and colored lines represent the position of individual cells over time. Data set (x, y, z, time) has the dimensions 164 microns × 164 microns × 40 microns × 25 minutes. Corresponds to Fig. 2a. A typical slow meandering thymocyte (black track near center), and a rare rapid directional thymocyte (black track near bottom), are highlighted. (AVI 27309 kb)

  2. Supplementary Video 2

    Rapid, directional migration of thymocytes expressing a positively selected TCR. Real-time imaging of thymocytes expressing GFP and a positively selected TCR (P14) in the cortex of intact thymic lobes. Green represents the fluorescent signal from GFP+ thymocytes and colored lines represent the position of individual cells over time. Data set (x, y, z, time) has the dimensions 164 microns × 164 microns × 40 microns × 25 minutes. Corresponds to Fig. 2b. Note the large proportion of rapid, directional thymocytes. (AVI 26643 kb)

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Figure 1: Compartmentalization of the adult thymus.
Figure 2: Positive selection–driven changes in thymocyte motility.