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Crawling of effector T cells on extracellular matrix: role of integrins in interstitial migration in inflamed tissues

Cellular & Molecular Immunology volume 11, pages 1–4 (2014)Cite this article

T cells are one of the most migratory cells in the body. The development and function of T cells depend on their interaction with other cells, which is, in turn, dependent on optimal cell migration. T cells migrate largely in three different ways: rapid distribution via blood vessels through hemodynamic movement, transendothelial migration and interstitial movement. Transendothelial migration involves sequential activation of selectins, chemokine receptors and integrin molecules expressed by migrating T cells, leading to extravasation from blood vessel into local tissue environments. Interstitial migration involves T-cell migration within a local tissue environment. While the critical roles of integrins for transendothelial migration are well established, integrins appear to be largely dispensable for interstitial migration in three-dimensional extracellular matrix (ECM).1,2,3 A leading theory is an actin-myosin-based and non-adhesive ‘crawling and squeezing amoeboid motility’. Pertussis toxin-sensitive signaling from G protein-coupled receptors, activated mainly by chemoattractants regulates interstitial migration. It is thought that interstitial migration involves both hapto- and chemo-taxis (or –kinesis), but the exact migration mechanisms specific for cell types, tissues and conditions remain unclear. Because of the roles of integrins in cell adhesion to extracellular matrix proteins such as collagens, fibronectin and vitronectin, searches for integrins that can guide cell migration in specialized tissues and conditions continued. Recently, Overstreet et al.4 reported that αV-containing integrins play important roles in interstitial T-cell migration in inflamed tissues.4

Overstreet et al. utilized multiphoton microscopy to examine T-cell migration in the inflamed skin. Multiphoton microscopy is an ideal tool to determine 3D T-cell migration in tissues. The advantages include deep tissue imaging up to ∼500 µm in live unfixed tissues. In soft tissues like, brain tissues, even deeper imaging up to ∼1 mm is possible. Multiphoton microscopy involves relatively faster resonance scanners which can readily acquire images of T cells migrating at speeds up to 30 µm/min. However, it is not the best instrument to image faster moving cells on blood vessels, which can be better imaged by other methods such as charge-coupled device camera-based spinning disk microscopy. Multiphoton microscopy is particularly useful in multichannel intravital imaging of cell–cell interaction in tissues of live animals. T cells are chemically labeled with membrane dyes or genetically labeled with fluorescent proteins, which are excited by one to two infrared lasers. Sophisticated software such as Imaris and Volocity are used for 3D image analysis.

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Acknowledgements

I thank B Ramsey and L Friesen at Purdue for helpful inputs. This study was supported, in part, from grants from NIH (R01AI074745, R01DK076616 and R01AI080769), National Multiple Sclerosis Society, and Michael J. Fox Foundation for Parkinson's research to CHK.

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  1. Department of Comparative Pathobiology; Weldon School of Biomedical Engineering, Laboratory of Immunology and Hematopoiesis, Purdue Center for Cancer Research; Purdue University,

    Chang H Kim

  2. Weldon School of Biomedical Engineering, Purdue Center for Cancer Research, West Lafayette, 47907, IN, USA

    Chang H Kim

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Correspondence to Chang H Kim.

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Kim, C. Crawling of effector T cells on extracellular matrix: role of integrins in interstitial migration in inflamed tissues. Cell Mol Immunol 11, 1–4 (2014). https://doi.org/10.1038/cmi.2013.47

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