Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide |
| |
Authors: | Siegert Stefanie Huang Hsin-Ying Yang Chen-Ying Scarpellino Leonardo Carrie Lucie Essex Sarah Nelson Peter J Heikenwalder Matthias Acha-Orbea Hans Buckley Christopher D Marsland Benjamin J Zehn Dietmar Luther Sanjiv A |
| |
Institution: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|