The ontogeny of T cells in T-cell receptor (TCR) transgenic mice, which express a transgenic
αβ heterodimer, specific for the male (H-Y) antigen in association with H-2Db, was determined. The transgenic α chain was expressed on about 10% of the fetal thymocytes on day
14 of gestation. About 50% of day-15 fetal thymocytes expressed both α and β transchains and virtually all fetal thymocytes expressed the transgenicαβ
heterodimer by day 17. The
early expression of the transgenic TCR on CD4-8- thymocytes prevented the development of γδ cells, and led to accelerated growth of thymocytes and an earlier expression of CD4 and
CD8 molecules. Up to day 17, no significant differences in T-cell development could be
detected between female and male thymuses. By day 18 of gestation, the male transgenic
thymus contained more CD4-8- thymocytes than the female transgenic thymus. The
preponderance of CD4-8- thymocytes in the male transgenic thymus increased until birth
and was a consequence of the deletion of the CD4+8+ thymocytes and their CD4-8+ precursors. By the time of birth, the male transgenic thymus contained half the number of cells as the female transgenic thymus. The deletion of autospecific precursor cells in the male
transgenic mouse began only at day 18 of gestation, despite the fact that the ligand could
already be detected by day 16.The preferential accumulation of CD4-8+ T cells, which expressed a high density of the transgenic TCR, occurred only after birth and was .obvious in 6-week-old female thymus.
These data support the hypothesis that the positive selection of T cells expressing this transgenic
heterodimer may involve two steps, i.e., the commitment of CD4+8+ thymocytes to the
CD4-8+ lineage following the interaction of the transgenic TCR with restricting major histocompatibility
molecules, followed by a slow conversion of CD4+8+ thymocytes into CD4-8+
T cells.In normal mice, the precursors of CD+4+8 and single positive thymocytes have the
CD4-8- CD3-J11d+ (or M1/69 +) phenotype. Because of the early expression of the transgenic
αβ heterodimer, this population was not detected in adult transgenic mice. All CD4-8- M1/
69+ cells expressed the transgenic receptor associated with CD3 and could be readily grown
in media containing T-cell lectins and interleukin 2.