Functional maturation of mouse CD4+CD8- thymocytes induced by medullary-type thymus epithelial cells

Murine CD4⁺CD8^- (CD4SP) thymocyte subset is a heterogeneous population, in which the Qa-2^- cells are less functional, whereas the Qa-2⁺ cells are fully functional. Evidence is provided here that the transition from Qa-2^- to Qa-2⁺ CD4SP thymocytes is an intrathymic process of differentiation induced by thymic medullary-type epithelial cells. The separated Qa-2^-CD4SP could be induced to express Qa-2 molecules up to 84%- 89% of the total viable celb after cocultured for 3d with MTEC1 cells, a murine thymic medullary type epithelial cell line established in our laboratory. Kinetic study showed that both the percentage of Qa-2⁺ cells and the density of the expressed Qa-2 molecules on CD4SP thymocytes induced by MTEC1 were progressively increasing in 72-h cultures. The MTECl-induced Qa-2⁺CD4SP thymocytes were fully functional, which exhibited capabilities of proliferation and cytokine secretion in response to Con A stimulation as high as those of freshly isolated Qa-2⁺CD4SP thymocytes. The profile of cytokines secreted by MTECl-induced Qa-2⁺CD4SP thymocytes was Thy 0 type specified by the production of IL-2, IL-4 and IL-6. The results suggest that Qa-2^-CD4SP thymocytes may give rise to the Qa-2⁺CD4SP thymocytes, and acquire fully functional competence in thymic medulla under the foster of local epithelial cells.