Interleukin 2 signaling is required for CD4(+) regulatory T cell function.
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-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.
Furtado
Gláucia C
GC
Program of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
Curotto de Lafaille
Maria A
MA
Kutchukhidze
Nino
N
Lafaille
Juan J
JJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D007073:Immunoglobulin E / Q000097:blood; D007376:Interleukin-2 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000502:physiology
D007376:Interleukin-2; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D007073:Immunoglobulin E