FUNCTIONAL MATURATION OF MOUSE CD4(-) THYMOCYTES INDUCED BY MEDULLARY-TYPE THYMUS EPITHELIAL-CELLS()CD8()

Murine CD4(+)CD8(-)(CD4SP) thymocyte subset is a heterogeneous populat ion, in which the Qa-2(-) ails are less functional, whereas the Qa-2() cells are fully functional. Evidence is provided here that the trans ition from Qa-2(-) to Qa-2(+) CD4SP thymocytes is an intrathymic proce ss of differentiation induced by thymic medullary-type epithelial cell s. The separated Qa-2(-)CD4SP could be induced to express Qa-2 molecul es up to 84%-89% of the total viable cells after cocultured for 3d wit h MTEC1 cells, a murine thymic medullary type epithelial cell line est ablished in our laboratory. Kinetic study showed that both the percent age of Qa-2(+) cells and the density of the expressed Qa-2 molecules o n CD4SP thymocytes induced by MTECl were progressively increasing in 7 2-h cultures. The MTEC1-induced Qa-2(+)CD4SP thymocytes were fully fun ctional, which exhibited capabilities of proliferation and cytokine se cretion in response to Con A stimulation as high as those of freshly i solated Qa-2(+)CD4SP thymocytes. The profile of cytokines secreted by MTEC1-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(-)CD4 SP thymocytes may give rise to the Qa-2(+)CD4SP thymocytes, and acquir e fully functional competence in thymic medulla under the foster of lo cal epithelial cells.