Treg-cell specific deletion of Ctla4 has revealed a critical role of CTLA-4 in Treg-cell specific function at steady-state: Loss of CTLA-4 in Treg cells results in fatal autoimmune disease, largely phenocopying total Treg-cell deficiency and suggesting that CTLA-4 is critical in maintaining immunological tolerance of a polyclonal T-cell repertoire (12). Here, CTLA4 is linked to autoimmune disease.