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

By G. Furtado, M. A. D. de Lafaille, N. Kutchukhidze, J. Lafaille. Journal of Experimental Medicine, 2002

702 citations recorded by the source corpus.

Mice deficient in interleukin (IL)-2 production or the IL-2 receptor α or β 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-2Rα (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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/ad2d8c15858f4d673ab9f76cd2811c93aa7d987b

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In Immunology

1. S. Rosenberg
2. N. Restifo
3. E. Shevach
4. C. Piccirillo
5. L. Gattinoni
6. A. Thornton
7. B. Blazar
8. D. Palmer

Citations in the corpus

• Cytokines in cancer pathogenesis and cancer therapy (2004, background): “; unfortunately, tumour responses are reduced, possibly because of the expansion of regulatory T cells that, paradoxically, suppress the intended antitumour respons”
• Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. (2008, unknown): “and Klein, 2005; Fontenot et al., 2005a; Furtado et al., 2002 ).”
• Adoptive immunotherapy for cancer: building on success (2006, background): “Perhaps more importantly, IL-2 is essential for the maintenance of peripheral self-toleranc”
• Interleukin-2 Receptor Signaling: At the Interface between Tolerance and Immunity (2010, unknown): “One study showed that providing IL-2 to IL-2-deficient peripheral T cells resulted in production of CD4+CD25+ T cells with suppressive properties (Furtado et al., 2002).”
• Natural and Induced CD4+CD25+ Cells Educate CD4+CD25− Cells to Develop Suppressive Activity: The Role of IL-2, TGF-β, and IL-101 (2004, background): “Signaling through CD122 is essential for the suppressive activity of CD4 CD25 cells (15,16).”
• IL-2 Receptor β-Dependent STAT5 Activation Is Required for the Development of Foxp3+ Regulatory T Cells1 (2007, background): “ample, studies by Lafaille and colleagues (9) demonstrated that the transfer of CD4 T cells from IL-2 / mice could prevent auto-”
• Cutting Edge: IL-2 Is Critically Required for the In Vitro Activation of CD4+CD25+ T Cell Suppressor Function (2004, background): “(8) demonstrated that CD4 T cells from IL-2 / mice protected”
• CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells (2005, background): “Lack of Treg cells, due to absence of IL-2 signaling, leads to uncontrolled CD4 T cell proliferation and activation, which paradoxically is not dependent on IL-2 (15, 21, 31, 51) However, even though IL-2 / mice get autoimmune disease, adoptive transfer of IL-2-deficient Th cells was unable to help ”