J Exp Med 2002 Sep 16;196(6):851-7
Furtado GC, De Lafaille MA, Kutchukhidze N, Lafaille JJ.
Program of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine. Department of Pathology, New York University School of Medicine, New York, NY 10016.
Mice deficient in interleukin (IL)-2 production or the IL-2 receptor alpha or beta 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-2Ralpha (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.