TGF-β Signalling Is Required for CD4+ T Cell Homeostasis But Dispensable for Regulatory T Cell Function

Abstract

Author SummaryTGF-β is a cytokine thought to be critical for the maintenance and function of tolerance in the immune system. In many studies the disruption of TGF-β signalling in CD4+ T cells (a type of white blood cell that coordinates immune responses) has resulted in autoimmune syndromes. We show here that the induced removal of this cytokine's receptor from these specialised blood cells results in an astonishingly mild outcome. Contrary to expectations, the number of regulatory T cells is actually increased, and we find that these cells are not dependent on TGF-β signalling. We also show that removal of the receptor from mature CD4+ T cells does not lead to lethal autoinflammation; only when we removed the receptor during development of the cells did we see the characteristic lethal multi-organ inflammation reported previously in constitutive models of TGF-β receptor ablation. In summary, our findings indicate that although TGF-β regulates maintenance of mature CD4+ T cells, its signals are dispensable for immune tolerance within this cell population.