The Journal of Experimental Medicine
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Published 16 September 2002. doi:10.1084/jem.20020190
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© Rockefeller University Press, 0022-1007/2002/9/851/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 6, September 16, 2002 851-857

Brief Definitive Report

 Interleukin 2 Signaling Is Required for CD4+ Regulatory T Cell Function

Gláucia C. Furtado1, Maria A. Curotto de Lafaille1, Nino Kutchukhidze1 and Juan J. Lafaille1,2

1 Program of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine
2 Department of Pathology, New York University School of Medicine, New York, NY 10016

Address correspondence to Juan J. Lafaille, Program of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Ave., New York, NY 10016. Phone: 212-263-1489; Fax: 212-263-5711; E-mail: lafaille{at}saturn.med.nyu.edu

Mice deficient in interleukin (IL)-2 production or the IL-2 receptor {alpha} or ß chains develop a lethal autoimmune syndrome. CD4+ regulatory T cells have been shown to prevent autoimmune diseases, allograft rejection, and to down-regulate antibody responses against foreign antigens. To assess the role of IL-2 in the generation and function of regulatory T cells, we transferred CD4+ T cells from mice genetically deficient in IL-2 or IL-2R{alpha} (CD25) expression. A small number of splenic or thymic CD4+ T cells from IL-2 knockout mice can protect mice from spontaneous experimental autoimmune encephalomyelitis (EAE). In contrast, splenic or thymic CD4+ T cells from CD25 knockout donor mice conferred little or no protection. We conclude that T cells with regulatory potential can develop, undergo thymic selection, and migrate to the peripheral lymphoid organs in the absence of IL-2, and do not protect from disease by means of IL-2 secretion. However, IL-2 signaling in regulatory T cells is essential for their protective function. Altogether, our results favor a model whereby IL-2 induces regulatory T cell activity.

Key Words: CD4+ T lymphocytes • immune tolerance • encephalomyelitis • autoimmunity • hypersensitivity


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