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