Requirements for T lymphocyte migration in explanted lymph nodes

Julie H. Huang, L. Isabel Cárdenas-Navia, Charles C. Caldwell, Troy J Plumb, Caius G. Radu, Paulo N. Rocha, Tuere Wilder, Jonathan S. Bromberg, Bruce N. Cronstein, Michail Sitkovsky, Mark W. Dewhirst, Michael L. Dustin

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Abstract

Although the requirements for T lymphocyte homing to lymph nodes (LNs) are well studied, much less is known about the requirements for T lymphocyte locomotion within LNs. Imaging of murine T lymphocyte migration in explanted LNs using two-photon laser-scanning fluorescence microscopy provides an opportunity to systematically study these requirements. We have developed a closed system for imaging an intact LN with controlled temperature, oxygenation, and perfusion rate. Naive T lymphocyte locomotion in the deep paracortex of the LN required a perfusion rate of > 13 μm/s and a partial pressure of O2 (pO2) of > 7.4%. Naive T lymphocyte locomotion in the subcapsular region was 38% slower and had higher turning angles and arrest coefficients than naive T lymphocytes in the deep paracortex. T lymphocyte activation decreased the requirement for pO2, but also decreased the speed of locomotion in the deep paracortex. Although CCR7-/- naive T cells displayed a small reduction in locomotion, systemic treatment with pertussis toxin reduced naive T lymphocyte speed by 59%, indicating a contribution of Gαi-mediated signaling, but involvement of other G protein-coupled receptors besides CCR7. Receptor knockouts or pharmacological inhibition in the adenosine, PG/lipoxygenase, lysophosphatidylcholine, and sphingosine-1-phosphate pathways did not individually alter naive T cell migration. These data implicate pO2, tissue architecture, and G-protein coupled receptor signaling in regulation of naive T lymphocyte migration in explanted LNs.

Original languageEnglish (US)
Pages (from-to)7747-7755
Number of pages9
JournalJournal of Immunology
Volume178
Issue number12
DOIs
Publication statusPublished - Jun 15 2007

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Huang, J. H., Cárdenas-Navia, L. I., Caldwell, C. C., Plumb, T. J., Radu, C. G., Rocha, P. N., ... Dustin, M. L. (2007). Requirements for T lymphocyte migration in explanted lymph nodes. Journal of Immunology, 178(12), 7747-7755. https://doi.org/10.4049/jimmunol.178.12.7747