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Siegert, S.* ; Huang, H.Y.* ; Yang, C.Y.* ; Scarpellino, L.* ; Carrie, L.* ; Essex, S.* ; Nelson, P.J. ; Heikenwälder, M.* ; Acha-Orbea, H.* ; Buckley, C.D.* ; Marsland, B.J.* ; Zehn, D.* ; Luther, S.A.*

Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide.

PLoS ONE 6:e27618 (2011)
Verlagsversion Volltext DOI
Open Access Gold
Creative Commons Lizenzvertrag
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
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter mesenchymal stem-cells; experimental autoimmune encephalomyelitis; regulatory dendritic cells; stromal cells; steady-state; differentiation; lymphocytes; homeostasis; chemokines; antigen
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 6, Heft: 11, Seiten: , Artikelnummer: e27618 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed