The Journal of Experimental Medicine
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Published online January 16, 2007
doi:10.1084/jem.20061198
The Journal of Experimental Medicine, Vol. 204, No. 1, 65-71
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Villarino et al.
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BRIEF DEFINITIVE REPORT

 Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals

Alejandro V. Villarino1, Cristina M. Tato2, Jason S. Stumhofer1, Zhengju Yao2, Yongzhi K. Cui3, Lothar Hennighausen3, John J. O'Shea2, and Christopher A. Hunter1

1 Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
2 Laboratory of Molecular Immunology and Inflammation, National Institute of Arthritis, Muscoskeletal and Skin Diseases, and 3 Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892

CORRESPONDENCE Christopher A. Hunter: chunter{at}vet.upenn.edu OR Alejandro V. Villarino: alejandro.villarino{at}ucsf.edu

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 {gamma} 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.

A.V. Villarino's present address is Dept. of Pathology, University of California San Francisco School of Medicine, San Francisco, CA 94143.


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