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PMID: 22786769 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 189 ·No. 4 ·2012-08-15 ·Pages 1780-91

Cheng G, Yuan X, Tsai MS, Podack ER, Yu A, Malek TR

Abstract

Thymic-derived natural T regulatory cells (Tregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs has been shown to express Klrg1, but it remains unclear as to what extent Klrg1 defines a unique Treg subset. In this study, we show that Klrg1(+) Tregs represent a terminally differentiated Treg subset derived from Klrg1(-) Tregs. This subset is a recent Ag-responsive and highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1(+) Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8(+) T effector cells. Our findings suggest that an important pathway driving Ag-activated conventional T lymphocytes also operates for Tregs.

MeSH Terms
Adoptive Transfer Animals Cell Differentiation/immunology Flow Cytometry Gene Expression Profiling Lectins, C-Type Lymphocyte Activation/immunology Mice Mice, Inbred C57BL Mice, Transgenic Microarray Analysis Receptors, Immunologic/immunology,metabolism Receptors, Interleukin-2/immunology,metabolism Signal Transduction/immunology T-Lymphocyte Subsets/cytology,immunology,metabolism T-Lymphocytes, Regulatory/cytology,immunology,metabolism
Chemicals
Klrg1 protein, mouse Lectins, C-Type Receptors, Immunologic Receptors, Interleukin-2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cheng Guoyan
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
Yuan Xiaomei
Tsai Matthew S
Podack Eckhard R
Yu Aixin
Malek Thomas R
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.1103768
Published
2012-08-15
Epub
2012-00-11
Pages
1780-91
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC3411868
Subset
IM
Grants
NCI NIH HHS · R01CA45957 · United States
NIAID NIH HHS · R01 AI055815 · United States
NCI NIH HHS · R01 CA045957 · United States
NIAID NIH HHS · R56AI100289 · United States
NIAID NIH HHS · R01AI055815 · United States
NIAID NIH HHS · R56 AI100289 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.1103768 PMC Full Text View journal details
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