Requirements for T Lymphocyte Migration in Explanted Lymph Nodes
Autor: | Jonathan S. Bromberg, Caius G. Radu, Tuere Wilder, Mark W. Dewhirst, Michail Sitkovsky, L. Isabel Cárdenas-Navia, Bruce N. Cronstein, Troy J. Plumb, Michael L. Dustin, Julie H. Huang, Charles C. Caldwell, Paulo Novis Rocha |
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Rok vydání: | 2007 |
Předmět: |
Receptors
CCR7 Adenosine Receptor Adenosine A2A Naive T cell Partial Pressure T-Lymphocytes Immunology C-C chemokine receptor type 7 GTP-Binding Protein alpha Subunits Gi-Go Biology Pertussis toxin Mice Cell Movement medicine Animals Immunology and Allergy Receptor Mice Knockout Naive T-Lymphocyte T lymphocyte Molecular biology Adenosine A2 Receptor Antagonists Oxygen Perfusion Receptors Chemokine Lymph Nodes Lymph medicine.drug |
Zdroj: | Scopus-Elsevier |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.178.12.7747 |
Popis: | 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. |
Databáze: | OpenAIRE |
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