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Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide.
- Source :
-
PloS one [PLoS One] 2011; Vol. 6 (11), pp. e27618. Date of Electronic Publication: 2011 Nov 14. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cell Proliferation
Dendritic Cells cytology
Dendritic Cells immunology
Gene Expression Regulation, Enzymologic immunology
Interferon-gamma metabolism
Mice
Nitric Oxide Synthase Type II deficiency
T-Lymphocytes immunology
T-Lymphocytes metabolism
Fibroblasts cytology
Fibroblasts metabolism
Lymph Nodes cytology
Nitric Oxide biosynthesis
T-Lymphocytes cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22110693
- Full Text :
- https://doi.org/10.1371/journal.pone.0027618