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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)
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Open Access Gold
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords mesenchymal stem-cells; experimental autoimmune encephalomyelitis; regulatory dendritic cells; stromal cells; steady-state; differentiation; lymphocytes; homeostasis; chemokines; antigen
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 6, Issue: 11, Pages: , Article Number: e27618 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed