Is autoimmunity associated with Foxp3 mutation due to TR-cell deficiency?
Lack of TR cells in Foxp3-deficient mice is the cause of the lymphoproliferative syndrome. Evidence for this is provided by the substantial reduction in this syndrome upon neonatal transfer of a small number of wild-type TR cells23. It is noteworthy that the antigen-specific responses of mouse non-regulatory CD4+ and CD8+ T cells expressing or lacking the Foxp3 gene are indistinguishable when measured by clonal expansion and cytokine production in vivo and by cognate peptide-dose response and co-stimulation dependence in vitro. Importantly, temporal Foxp3 upregulation is not observed in these cells during the course of conventional antigen-specific immune responses. These observations, combined with the identical onset and progression of autoimmune disease in mice with germline and T-cell-specific ablation of the Foxp3 gene, provide further proof that TR-cell deficiency in mice results in a major breakdown of self tolerance and autoimmune pathology affecting multiple organs31.Because t
