INTERMEDIATE STEPS IN POSITIVE SELECTION - DIFFERENTIATION OF CD4+8(INT) TCR(INT) THYMOCYTES INTO CD4-8+TCR(HI) THYMOCYTES

The differentiation potential of putative intermediates between CD4(+)8(+) thymocytes and mature T cells has been examined. Such intermediate populations were sorted, in parallel with CD4(+)8(+) thymocytes, from three types of C57BL/6 mice: major histocompatibility complex (MHC) class II-deficient mice, mice transgenic for an alpha/beta T cell receptor (TCR) restricted by class I MHC and normal mice. The sorted populations were then transferred into the thymus of nonirradiated C57BL/Ka mice differing in Thy 1 allotype, and the progeny of the transferred cells were analyzed 2 d later. Surprisingly, with all three types of donor mice, a major proportion of the CD4(+)8(int)TCR(int)-derived progeny were found to be CD4(-)8(+)TCR(hi) cells, thus delineating a new alternative pathway for development of the CD8 lineage. In contrast, the transfer of CD4(int)8(+)TCR(int) thymocytes produced CD4(-)8(+)TCR(hi) cells but no significant proportion of CD4(+)8(-)TCR(hi) cells, suggesting that there is no equivalent alternative pathway for the CD4 lineage. The results negate some of the evidence for a stochastic/selective model of lineage commitment, and point to an asymmetry in the steps leading to CD4(-)8(+) versus CD4(+)8(-) T cells.