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Nat Immunol. 2016 Dec;17(12):1436-1446. doi: 10.1038/ni.3578. Epub 2016 Oct 3.

Suppression by TFR cells leads to durable and selective inhibition of B cell effector function.

Author information

1
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
2
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
3
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
5
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
6
FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
7
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Abstract

Follicular regulatory T cells (TFR cells) inhibit follicular helper T cell (TFH cell)-mediated antibody production. The mechanisms by which TFR cells exert their key immunoregulatory functions are largely unknown. Here we found that TFR cells induced a distinct suppressive state in TFH cells and B cells, in which effector transcriptional signatures were maintained but key effector molecules and metabolic pathways were suppressed. The suppression of B cell antibody production and metabolism by TFR cells was durable and persisted even in the absence of TFR cells. This durable suppression was due in part to epigenetic changes. The cytokine IL-21 was able to overcome TFR cell-mediated suppression and inhibited TFR cells and stimulated B cells. By determining mechanisms of TFR cell-mediated suppression, we have identified methods for modulating the function of TFR cells and antibody production.

PMID:
27695002
PMCID:
PMC5502675
DOI:
10.1038/ni.3578
[Indexed for MEDLINE]
Free PMC Article

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