Stochastic coreceptor shut-off 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 CD4lo8+ 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 CD8lo step for the former and at the CD4+8+ double-positive stage for the latter.
Lucas
B
B
Unité 345 Institut de la Santé et de la Recherche Médicale, CHU Necker-Enfants, Paris, France.
Vasseur
F
F
Penit
C
C
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001973:Bromodeoxyuridine