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J Exp Med. 2017 Dec 4;214(12):3519-3530. doi: 10.1084/jem.20162084. Epub 2017 Oct 24.

Identification and characterization of T reg-like cells in zebrafish.

Author information

1
Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA.
2
Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.
3
Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.
4
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.
5
Harvard Stem Cell Institute, Cambridge, MA.
6
Department of Biological Sciences, California State University, Chico, CA.
7
Department of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA.
8
Departments of Surgery and Medicine, Weill Cornell Medical College, New York, NY.
9
Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA craig.ceol@umassmed.edu.

Abstract

Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg-deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there. To begin to address these issues, we sought to identify T reg cells in zebrafish, a model system that provides unparalleled advantages in live-cell imaging and high-throughput genetic analyses. Using a FOXP3 orthologue as a marker, we identified CD4-enriched, mature T lymphocytes with properties of T reg cells. Zebrafish mutant for foxp3a displayed excess T lymphocytes, splenomegaly, and a profound inflammatory phenotype that was suppressed by genetic ablation of lymphocytes. This study identifies T reg-like cells in zebrafish, providing both a model to study the normal functions of these cells in vivo and mutants to explore the consequences of their loss.

PMID:
29066577
PMCID:
PMC5716030
DOI:
10.1084/jem.20162084
[Indexed for MEDLINE]
Free PMC Article

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