Lukacs-Kornek, V;
Malhotra, D;
Fletcher, AL;
Acton, SE;
Elpek, KG;
Tayalia, P;
Collier, A-R;
(2011)
Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes.
Nature Immunology
, 12
(11)
pp. 1096-1104.
10.1038/ni.2112.
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Abstract
Fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) are nonhematopoietic stromal cells of lymphoid organs. They influence the migration and homeostasis of naive T cells; however, their influence on activated T cells remains undescribed. Here we report that FRCs and LECs inhibited T cell proliferation through a tightly regulated mechanism dependent on nitric oxide synthase 2 (NOS2). Expression of NOS2 and production of nitric oxide paralleled the activation of T cells and required a tripartite synergism of interferon-γ, tumor necrosis factor and direct contact with activated T cells. Notably, in vivo expression of NOS2 by FRCs and LECs regulated the size of the activated T cell pool. Our study elucidates an as-yet-unrecognized role for the lymph node stromal niche in controlling T cell responses.
| Type: | Article |
|---|---|
| Title: | Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ni.2112 |
| Publisher version: | http://dx.doi.org/10.1038/ni.2112 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions |
| Keywords: | Animals, Cell Growth Processes, Cell Movement, Cells, Culture, Clonal Selection, Antigen-Mediated, Endothelium, Lymphatic, Intercellular Junctions, Interferon-gamma, Lymph Nodes, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Nitric Oxide, Nitric Oxide Synthase Type II, Stromal Cells, T-Lymphocytes, Transgenes, Tumor Necrosis Factor-alpha |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1387315 |
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