REGULATION OF EARLY T-CELL DEVELOPMENT BY THE ENGAGEMENT OF TCR-BETA COMPLEX EXPRESSED ON FETAL THYMOCYTES FROM TCR-BETA-TRANSGENIC SCID MICE

Transgenic expression of the beta-chain of T cell antigen-receptor (TC R) is known to induce the generation of CD4(+)CD8(+) thymocytes in the immunodeficient scid mouse, in which thymocyte development is otherwi se arrested at CD4(-)CD8(-) cells. It is not clear, however, whether o r not the thymocyte development is controlled by ligand engagement of the TCR-beta complex on the cell surface. In the present study, we hav e examined how the engagement by Ab of the TCR-beta complex expressed on the TCR-beta-transgenic scid fetal thymocytes can regulate the gene ration of CD4(+)CD8(+) thymocytes. Organ cultures of CD4(-)CD8(-) day 14 fetal thymocytes from the TCR-beta-transgenic scid mice resulted in the generation of CD4(-)CD8(+) and then CD4(+)CD8(+) cells. The initi al step from CD4(-)CD8(-) cells to CD4(-)CD(8)+ cells was enhanced by the addition of anti-TCR-beta Ab, whereas the subsequent step from CD4 (-)CD8(+) cells to CD4(+)CD8(+) cells was markedly inhibited by anti-T CR-beta Ab. These results indicate that ligand engagement of the TCR-b eta complex can positively and negatively regulate the early thymocyte development. Moreover, the finding that engagement of TCR-beta comple x inhibits the generation of CD4(+)CD8(+) cells suggests that the indu ction of CD4(+)CD8(+) thymocytes by the TCR-beta transgene is not an i mmediate consequence of cell-surface engagement of the TCR-beta comple x but requires liberation from the continued TCR-beta signaling.