Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative feedback loop that functions autonomously or in collaboration with other common γ chain (IL-4 and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this model for cytokine-dependent regulation, they also demonstrate that the inhibitory effect can be mediated by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6. Collectively, these findings establish that IL-2 production is limited by a network of autocrine and paracrine signals that are readily available during acute inflammatory responses and, thus, provide a cellular and molecular basis for its transient pattern of expression.
Skip Nav Destination
Article navigation
22 January 2007
Brief Definitive Report|
January 16 2007
Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
Alejandro V. Villarino,
Alejandro V. Villarino
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
Search for other works by this author on:
Cristina M. Tato,
Cristina M. Tato
2Laboratory of Molecular Immunology and Inflammation, National Institute of Arthritis, Muscoskeletal and Skin Diseases,
Search for other works by this author on:
Jason S. Stumhofer,
Jason S. Stumhofer
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
Search for other works by this author on:
Zhengju Yao,
Zhengju Yao
2Laboratory of Molecular Immunology and Inflammation, National Institute of Arthritis, Muscoskeletal and Skin Diseases,
Search for other works by this author on:
Yongzhi K. Cui,
Yongzhi K. Cui
3Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892
Search for other works by this author on:
Lothar Hennighausen,
Lothar Hennighausen
3Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892
Search for other works by this author on:
John J. O'Shea,
John J. O'Shea
2Laboratory of Molecular Immunology and Inflammation, National Institute of Arthritis, Muscoskeletal and Skin Diseases,
Search for other works by this author on:
Christopher A. Hunter
Christopher A. Hunter
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
Search for other works by this author on:
Alejandro V. Villarino
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
Cristina M. Tato
2Laboratory of Molecular Immunology and Inflammation, National Institute of Arthritis, Muscoskeletal and Skin Diseases,
Jason S. Stumhofer
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
Zhengju Yao
2Laboratory of Molecular Immunology and Inflammation, National Institute of Arthritis, Muscoskeletal and Skin Diseases,
Yongzhi K. Cui
3Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892
Lothar Hennighausen
3Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892
John J. O'Shea
2Laboratory of Molecular Immunology and Inflammation, National Institute of Arthritis, Muscoskeletal and Skin Diseases,
Christopher A. Hunter
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
CORRESPONDENCE Christopher A. Hunter: [email protected] OR Alejandro V. Villarino: [email protected]
A.V. Villarino's present address is Dept. of Pathology, University of California San Francisco School of Medicine, San Francisco, CA 94143.
Received:
June 06 2006
Accepted:
December 13 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (1): 65–71.
Article history
Received:
June 06 2006
Accepted:
December 13 2006
Citation
Alejandro V. Villarino, Cristina M. Tato, Jason S. Stumhofer, Zhengju Yao, Yongzhi K. Cui, Lothar Hennighausen, John J. O'Shea, Christopher A. Hunter; Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals . J Exp Med 22 January 2007; 204 (1): 65–71. doi: https://doi.org/10.1084/jem.20061198
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement