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TGF-β and IL-2 are two important cytokines in regulating the balance between regulatory T cells and conventional T cells, thus the homeostasis of the immune system.To investigate the synergetic role of these two cytokines on T cells, we crossed dnTGF-βRⅡ with CD25(-/-) mice to generate dnTGF-βRⅡ CD25(-/-) mice(abbreviated as Tg CD25(-/-) mice),in which IL-2 and TGF-β signals are both blocked in T cells.We found that this mice started to die at 3 weeks of age, and spontaneously developed systemic autoimmune diseases with a significant elevation of pathogenic T cells.