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Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes

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. Green open access

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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.ucl.ac.uk/id/eprint/1387315
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