The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function

Andrew N Macintyre; Valerie A Gerriets; Amanda G Nichols; Ryan D Michalek; Michael C Rudolph; Divino Deoliveira; Steven M Anderson; E Dale Abel; Benny J Chen; Laura P Hale; Jeffrey C Rathmell

doi:10.1016/j.cmet.2014.05.004

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The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function

Journal article

Open access

Peer reviewed

The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function

Andrew N Macintyre, Valerie A Gerriets, Amanda G Nichols, Ryan D Michalek, Michael C Rudolph, Divino Deoliveira, Steven M Anderson, E Dale Abel, Benny J Chen, Laura P Hale, …

Cell metabolism, Vol.20(1), pp.61-72

07/01/2014

DOI: 10.1016/j.cmet.2014.05.004

PMCID: PMC4079750

PMID: 24930970

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Abstract

CD4 T cell activation leads to proliferation and differentiation into effector (Teff) or regulatory (Treg) cells that mediate or control immunity. While each subset prefers distinct glycolytic or oxidative metabolic programs in vitro, requirements and mechanisms that control T cell glucose uptake and metabolism in vivo are uncertain. Despite expression of multiple glucose transporters, Glut1 deficiency selectively impaired metabolism and function of thymocytes and Teff. Resting T cells were normal until activated, when Glut1 deficiency prevented increased glucose uptake and glycolysis, growth, proliferation, and decreased Teff survival and differentiation. Importantly, Glut1 deficiency decreased Teff expansion and the ability to induce inflammatory disease in vivo. Treg cells, in contrast, were enriched in vivo and appeared functionally unaffected and able to suppress Teff, irrespective of Glut1 expression. These data show a selective in vivo requirement for Glut1 in metabolic reprogramming of CD4 T cell activation and Teff expansion and survival.

T-Lymphocytes, Regulatory - metabolism

Homeodomain Proteins - metabolism

Humans

Colitis - pathology

Glucose Transporter Type 1 - metabolism

Glucose Transporter Type 3 - metabolism

RNA, Messenger - metabolism

Transplantation, Homologous

T-Lymphocytes, Regulatory - immunology

CD4-Positive T-Lymphocytes - immunology

Glucose Transporter Type 3 - genetics

T-Lymphocytes, Helper-Inducer - immunology

T-Lymphocytes, Helper-Inducer - cytology

T-Lymphocytes, Regulatory - cytology

Colitis - immunology

T-Lymphocytes, Helper-Inducer - metabolism

Cell Survival

Mice, Inbred C57BL

CD4-Positive T-Lymphocytes - metabolism

Homeodomain Proteins - genetics

Mice, Knockout

Animals

CD4-Positive T-Lymphocytes - transplantation

Glucose Transporter Type 1 - genetics

Colitis - metabolism

Glucose - metabolism

Glycolysis

Mice

Mice, Inbred BALB C

Details

Title: Subtitle: The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function
Creators: Andrew N Macintyre - Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA
Valerie A Gerriets - Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA
Amanda G Nichols - Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA
Ryan D Michalek - Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA
Michael C Rudolph - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Divino Deoliveira - Division of Hematological Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, NC 27710, USA
Steven M Anderson - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
E Dale Abel - Fraternal Order of Eagles Diabetes Research Center, Division of Endocrinology and Metabolism, Department of Medicine, Carver College of Medicine University of Iowa, Iowa City, IA 52242, USA
Benny J Chen - Division of Hematological Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, NC 27710, USA
Laura P Hale - Department of Pathology, Duke University, Durham, NC 27710, USA
Jeffrey C Rathmell - Department of Pharmacology and Cancer Biology, Immunology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.20(1), pp.61-72
Publisher: United States
DOI: 10.1016/j.cmet.2014.05.004
PMID: 24930970
PMCID: PMC4079750
ISSN: 1550-4131
eISSN: 1932-7420
Grant note: U54 HL112311 / NHLBI NIH HHS R01 AI063345 / NIAID NIH HHS U01 HL087947 / NHLBI NIH HHS P01 HD038129 / NICHD NIH HHS T32 HD007186 / NICHD NIH HHS R01CA138482 / NCI NIH HHS R03 AI106835 / NIAID NIH HHS R01AI063345 / NIAID NIH HHS P01CA047741 / NCI NIH HHS R01 HL108006 / NHLBI NIH HHS P30 CA014236 / NCI NIH HHS R56AI102074 / NIAID NIH HHS R01 CA138482 / NCI NIH HHS P01 CA047741 / NCI NIH HHS U01HL087947 / NHLBI NIH HHS R56 AI102074 / NIAID NIH HHS R01HL108006 / NHLBI NIH HHS
Language: English
Date published: 07/01/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024420602771

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