title: Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes.
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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Lukacs-Kornek
authors.forename: Deepali
authors.initials: D
authors.lastname: Malhotra
authors.forename: Anne L
authors.initials: AL
authors.lastname: Fletcher
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Acton
authors.forename: Kutlu G
authors.initials: KG
authors.lastname: Elpek
authors.forename: Prakriti
authors.initials: P
authors.lastname: Tayalia
authors.forename: Ai-ris
authors.initials: AR
authors.lastname: Collier
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Turley
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated; D004729:Endothelium, Lymphatic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007365:Intercellular Junctions / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019076:Transgenes / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse