Th1 Cells Promote Thymic Epithelial Cell Apoptosis

Objective: Our research was aimed to primarily investigate the mechanism of apoptosis of thymic epithelial cells(TECs) induced by activated Th1 cells and the opposite effect mediated by doxycycline and thus, providing the experimential research basis for clinical T cell immune re-establishment.Methods: Th1 cells were induced by IL-12, IL-2 and anti-IL-4 from sorted CD4+ T cells in C57BL/6 mice. MTEC1 cells were co-cultured with Th1 cells or supernatants of Th1 cells respectively in the presence or absence anti-IFN-γ antibody, and the apoptosis of MTEC1 cells was determined by flow cytometry. To investigate whether activated Th1 cells could migrate to the thymus in the inflammatory condition and induce apoptosis of TECs, we injected CFSE labeled Th1 cells into the hearts of mice, the proportion of labeled cells of thymocytes was determined by flow cytometry. MTEC1 cells were treated with IFN-γ and different concentrations of doxycycline and their apoptosis were determined by flow cytometry, the protein levels of Trx2, Bcl-2 and Bax in MTEC1 cells were determined by western blot.Results: The apoptosis proportion of MTEC1 cells was increased when the cells were co-cultured with Th1 cells or their supernatants. The apoptosis of MTEC1 cells was partly reversed after being treated with anti-IFN-γ antibody. The labeled CD4+ T cells were detectable in the thymus, indicating that activated Th1 cells could migrate to the thymus. Our data demonstrated that the apoptosis proportion of MTEC1 cells was increased and the expression levels of Trx2 and Bcl-2 were decreased while that of Bax was increased after being MTEC1 cells were treated with IFN-γ. The apoptosis of MTEC1 cells was partly reversed while the expression level of Trx2 and Bcl-2 were increased when the cells were treated with doxycycline.Conclusions: Activated Th1 cells could migrate into the thymus and induce apoptosis of MTEC1 cells via secreting IFN-γ, resulting in inhibiting the expression of Trx2 and Bcl-2 while increasing the expression of Bax in part. The apoptosis of MTEC1 cells was partially reversed by doxycycline through upregulating the expression of Trx2 and Bcl-2.