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Tracking migration during human T cell development

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Abstract

Specialized microenvironments within the thymus are comprised of unique cell types with distinct roles in directing the development of a diverse, functional, and self-tolerant T cell repertoire. As they differentiate, thymocytes transit through a number of developmental intermediates that are associated with unique localization and migration patterns. For example, during one particular developmental transition, immature thymocytes more than double in speed as they become mature T cells that are among the fastest cells in the body. This transition is associated with dramatic changes in the expression of chemokine receptors and their antagonists, cell adhesion molecules, and cytoskeletal components to direct the maturing thymocyte population from the cortex to medulla. Here we discuss the dynamic changes in behavior that occur throughout thymocyte development, and provide an overview of the cell-intrinsic and extrinsic mechanisms that regulate human thymocyte migration.

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Abbreviations

AIRE:

Autoimmune regulator

BM:

Bone marrow

CMJ:

Cortical medullary junction

cTEC:

Cortical thymic epithelial cell

DCs:

Dendritic cells

DN:

CD4−CD8−, double negative

DP:

CD4+CD8+, double positive

ECM:

Extracellular matrix

FTY720:

Fingolimod

FTOC:

Fetal thymic organ culture

HPCs:

Hematopoietic progenitor cells

ICAM-1:

Intercellular adhesion molecule 1

IL2Rgamma:

IL2 receptor gamma chain

mTEC:

Medullary thymic epithelial cell

MS:

Multiple sclerosis

MST1:

Mammalian sterile 20-like protein kinase 1

NOD:

Non-obese diabetic

pMHC:

Peptide-MHC complexes

PNAd:

Peripheral node addressin

PSGL-1:

P-selectin glycoprotein ligand 1

SCID:

Severe combined immune deficiency

SP:

CD4+CD8− or CD8+CD4−, single positive

S1P:

Sphingosine-1-phosphate

TCR:

T cell receptor

TEC:

Thymic epithelial cell

TSLP:

Thymic stromal lymphopoietin

VCAM-1:

Vascular cell adhesion molecule 1

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Acknowledgments

We thank Brian Wiest, Claudia Brockmeyer, and Nadia Kurd for critical reading of the manuscript. This work was supported by the California Institute of Regenerative Medicine clinical fellowship TG2-01164 (to JH), post-doctoral training grant T1-00007 (to HJM), and grant RM1-01732 (to EAR).

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  1. Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, 142 Life Sciences Addition, #3200, Berkeley, CA, 94720-3200, USA

    Joanna Halkias, Heather J. Melichar, Kayleigh T. Taylor & Ellen A. Robey

  2. Division of Neonatology, Children’s Hospital and Research Center Oakland, 747 52nd Street, Oakland, CA, 94609, USA

    Joanna Halkias

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Halkias, J., Melichar, H.J., Taylor, K.T. et al. Tracking migration during human T cell development. Cell. Mol. Life Sci. 71, 3101–3117 (2014). https://doi.org/10.1007/s00018-014-1607-2

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