Identification and characterization of latency-associated peptide-expressing γδ T cells

Rafael M Rezende; Andre P da Cunha; Chantal Kuhn; Stephen Rubino; Hanane M'Hamdi; Galina Gabriely; Tyler Vandeventer; Shirong Liu; Ron Cialic; Natalia Pinheiro-Rosa; Rafael P Oliveira; Jellert T Gaublomme; Nikolaus Obholzer; James Kozubek; Nathalie Pochet; Ana M C Faria; Howard L Weiner

doi:10.1038/ncomms9726

Identification and characterization of latency-associated peptide-expressing γδ T cells

Nat Commun. 2015 Dec 8:6:8726. doi: 10.1038/ncomms9726.

Authors

Rafael M Rezende¹, Andre P da Cunha¹, Chantal Kuhn¹, Stephen Rubino¹, Hanane M'Hamdi^{1

2}, Galina Gabriely¹, Tyler Vandeventer¹, Shirong Liu¹, Ron Cialic¹, Natalia Pinheiro-Rosa³, Rafael P Oliveira³, Jellert T Gaublomme^{4

5}, Nikolaus Obholzer⁶, James Kozubek⁶, Nathalie Pochet^{6

7}, Ana M C Faria³, Howard L Weiner¹

Affiliations

¹ Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
² Rheumatology Unit, Department of Medicine at Karolinska University Hospital, Karolinska Institute, Solna, Stockholm 17177, Sweden.
³ Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31.270-901, Brazil.
⁴ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
⁵ Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.
⁶ Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
⁷ Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts 02142, USA.

Abstract

γδ T cells are a subset of lymphocytes specialized in protecting the host against pathogens and tumours. Here we describe a subset of regulatory γδ T cells that express the latency-associated peptide (LAP), a membrane-bound TGF-β1. Thymic CD27+IFN-γ+CCR9+α4β7+TCRγδ+ cells migrate to the periphery, particularly to Peyer's patches and small intestine lamina propria, where they upregulate LAP, downregulate IFN-γ via ATF-3 expression and acquire a regulatory phenotype. TCRγδ+LAP+ cells express antigen presentation molecules and function as antigen presenting cells that induce CD4+Foxp3+ regulatory T cells, although TCRγδ+LAP+ cells do not themselves express Foxp3. Identification of TCRγδ+LAP+ regulatory cells provides an avenue for understanding immune regulation and biologic processes linked to intestinal function and disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Activating Transcription Factor 3 / genetics
Activating Transcription Factor 3 / immunology
Adult
Animals
Animals, Congenic
Antigen-Presenting Cells
Colitis / immunology*
Cytokines / genetics
Cytokines / immunology*
Disease Models, Animal
Flow Cytometry
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / immunology
Humans
In Vitro Techniques
Interferon-gamma
Intestinal Mucosa / immunology*
Leukocytes, Mononuclear / immunology
Mice
Peyer's Patches / immunology*
Real-Time Polymerase Chain Reaction
Receptors, Antigen, T-Cell / immunology
Receptors, Antigen, T-Cell, gamma-delta / immunology*
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocyte Subsets / immunology*
T-Lymphocytes, Regulatory / immunology*
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / immunology*

Substances

Activating Transcription Factor 3
Atf3 protein, mouse
Cytokines
Forkhead Transcription Factors
Foxp3 protein, mouse
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell, gamma-delta
Transforming Growth Factor beta1
Interferon-gamma

Associated data

GEO/GSE73077

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding