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PLoS One. 2011;6(11):e27618. doi: 10.1371/journal.pone.0027618. Epub 2011 Nov 14.

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

Author information

1
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.

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.

PMID:
22110693
PMCID:
PMC3215737
DOI:
10.1371/journal.pone.0027618
[Indexed for MEDLINE]
Free PMC Article
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