Neoplastic thymic epithelial cells of human thymoma support T cell development from CD4−CD8− cells to CD4+CD8+ cells in vitro

Abstract

SUMMARY Human thymoma is a thymic epithelial cell tumour which often contains a large number of immature T cells and is frequently associated with autoimmune diseases. Since thymic epithelial cells play key roles in the development and selection of T cells in the normal thymus, we hypothesized that the neoplastic thymic epithelial cells of thymoma may support T cell differentiation in the tumour. We characterized CD4−CD8− cells in thymoma and applied an in vitro reconstitution culture system using the CD4−CD8− cells and the neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on 29.9 ± 12.2% of CD4−CD8− cells in thymoma. TCRγδ was expressed on 27.4 ± 15.1% of CD4−CD8− cells and CD19, a B cell marker, was expressed on 14.1 ± 23.1% of CD4−CD8− cells. CD4−CD8− cells expressed both IL-7R α-chain and common γ-chain. Purified CD4−CD8− cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single-positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. Furthermore, we examined the reconstitution culture using CD34+CD4−CD8− cells purified from normal infant thymus. The CD34+CD4−CD8− cells in normal thymus also differentiated to CD4+CD8+ cells in the allogeneic co-culture with the neoplastic epithelial cells of thymoma. These results indicate that the tumour cells of thymoma retain the function of thymic epithelial cells and can induce differentiation of T cells in thymoma.