Impaired Expansion of Regulatory T Cells in a Neonatal Thymectomy-Induced Autoimmune Mouse Model

Neonatal thymectomy (Tx) in certain mouse strains is known to induce organ-specific autoimmunity due to impaired functions of T cells, including Foxp3+ regulatory T (Treg) cells in the thymus. The precise mechanism underlying the induction of autoimmunity by neonatal Tx remains unclear. One possibility is that depletion of Treg cells breaks down peripheral tolerance. We examined the functions of Treg cells by using a murine Sjögren’s syndrome (SS) model, NFS/sld mice that underwent neonatal Tx. The ratio of Treg cells to effector memory phenotype T cells in Tx mice was significantly lower than that of non-Tx mice. In addition, in vitro induction of peripherally induced Treg cells by transforming growth factor-β (TGF-β) using naïve T cells from SS model mice was severely impaired. The mRNA expression of TGF-β receptor I, II, and Smad3 and -4 in the TGF-β-induced signal transduction pathway of Treg cells in this SS model were lower than those of control mice. In addition, Treg cells in this SS model exhibited an IFN-γ-producing Th1-like phenotype that resembled effector T cells. In conclusion, these results suggest that abnormal expansion and differentiation of Treg cells and inflammatory cytokines produced by Treg cells contribute to the development of autoimmunity.

© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/