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

PloS one (2011-11-24)
Stefanie Siegert, Hsin-Ying Huang, Chen-Ying Yang, Leonardo Scarpellino, Lucie Carrie, Sarah Essex, Peter J Nelson, Matthias Heikenwalder, Hans Acha-Orbea, Christopher D Buckley, Benjamin J Marsland, Dietmar Zehn, Sanjiv A Luther
RÉSUMÉ

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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1-Methyl-L-tryptophan, 95%