title: Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide.
abstract: Adaptive immune responses are initiated when T cells encounter antigen on dendritic cells (DC) in T zones of secondary lymphoid organs. T zones contain a 3-dimensional scaffold of fibroblastic reticular cells (FRC) but currently it is unclear how FRC influence T cell activation. Here we report that FRC lines and ex vivo FRC inhibit T cell proliferation but not differentiation. FRC share this feature with fibroblasts from non-lymphoid tissues as well as mesenchymal stromal cells. We identified FRC as strong source of nitric oxide (NO) thereby directly dampening T cell expansion as well as reducing the T cell priming capacity of DC. The expression of inducible nitric oxide synthase (iNOS) was up-regulated in a subset of FRC by both DC-signals as well as interferon-γ produced by primed CD8+ T cells. Importantly, iNOS expression was induced during viral infection in vivo in both LN FRC and DC. As a consequence, the primary T cell response was found to be exaggerated in Inos(-/-) mice. Our findings highlight that in addition to their established positive roles in T cell responses FRC and DC cooperate in a negative feedback loop to attenuate T cell expansion during acute inflammation.
authors: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors: Stefanie
authors: S
authors: Siegert
authors: Hsin-Ying
authors: HY
authors: Huang
authors: Chen-Ying
authors: CY
authors: Yang
authors: Leonardo
authors: L
authors: Scarpellino
authors: Lucie
authors: L
authors: Carrie
authors: Sarah
authors: S
authors: Essex
authors: Peter J
authors: PJ
authors: Nelson
authors: Matthias
authors: M
authors: Heikenwalder
authors: Hans
authors: H
authors: Acha-Orbea
authors: Christopher D
authors: CD
authors: Buckley
authors: Benjamin J
authors: BJ
authors: Marsland
authors: Dietmar
authors: D
authors: Zehn
authors: Sanjiv A
authors: SA
authors: Luther
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II