STOCHASTIC CORECEPTOR SHUTOFF IS RESTRICTED TO THE CD4 LINEAGE MATURATION PATHWAY

Kinetics of mature T cell generation in the thymus of normal or major histocompatibility complex (MHC) class I- or II-deficient mice were studied by the bromodeoxyuridine pulse labeling method. As previously described, the early activation and final maturation phases were found to be synchronous for the two T cell lineages, but CD4(+)8(-) cells were generated faster than CD4(-)8(+) cells in MHC class I- and II-deficient mice, respectively. CD8 downregulation started on day 2 after cell proliferation even in the absence of MHC class II expression. CD8 downregulation thus appears to be stochastic at its beginning. By contrast, CD4 shut-off was found totally instructive, as the generation of CD4(lo)8(+) cells with a high TCR density was not observed in class I-deficient mice. The analysis of the V(beta)14 TCR frequencies in CD4/8 subsets in normal and MHC-deficient mice confirmed that CD4 and CD8 generation pathways are not symmetrical. These findings show that commitment towards the CD4(+)8(-) or CD4(-)8(+) phenotype is controlled at the CD8(lo) step for the former and at the CD4(+)8(+) double-positive stage for the latter.