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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Growth Processes / genetics
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Cell Movement / genetics
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Cells, Cultured
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Clonal Selection, Antigen-Mediated*
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Endothelium, Lymphatic / immunology
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Endothelium, Lymphatic / metabolism*
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Endothelium, Lymphatic / pathology
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Intercellular Junctions / immunology
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Lymph Nodes / pathology
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Lymphocyte Activation / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / immunology
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Nitric Oxide Synthase Type II / metabolism*
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Stromal Cells / immunology
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Stromal Cells / metabolism*
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Stromal Cells / pathology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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T-Lymphocytes / pathology
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Transgenes / genetics
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Tumor Necrosis Factor-alpha
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Nitric Oxide
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Interferon-gamma
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse