Double-negative thymocyte subsets in CD3 zeta chain-deficient mice: absence of HSA+CD44-CD25- cells.
Double-negative (DN) thymocyte subsets were examined in mice deficient in the CD3 zeta chain (zeta-/-). The HSA+CD44-CD25- subset was found to be missing, and DN thymocytes seemed to differentiate directly from HSA+CD25+CD44- cells to double-positive (DP) cells. When fetal thymic ontogeny was examined, we found a marked difference between zeta-/- embryos and heterozygous littermates from embryonic day 17.5, in terms of CD25, CD4 and CD8 expression, and thymus size. The zeta-/- thymocytes failed to down-regulate CD25 and to expand exponentially. The cell cycle status of adult thymocyte subsets indicated that although the HSA+CD25-CD44- subset was missing, the CD25+ DN population contained normal numbers of cycling cells, and the CD25+ DP cells (which were not detectable in normal mice) contained 5-10% cells in G2/M+S. Taken together these data suggest that the CD3 zeta chain might have a specific role in the control of proliferation of DN thymocytes during T cell development. Our data clearly show that one can dissociate the signal for a CD25+ DN cell to differentiate (which occurs in the absence of CD3 zeta), from a signal to proliferate and from loss of cell surface CD25.
Crompton
T
T
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, University of Edinburgh, GB.
Moore
M
M
MacDonald
H R
HR
Malissen
B
B
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D051927:CD24 Antigen; D002352:Carrier Proteins / Q000096:biosynthesis / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D011506:Proteins / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051927:CD24 Antigen; D002352:Carrier Proteins; C497890:Cd24a protein, mouse; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing; C054979:antigen T cell receptor, zeta chain; C064658:RAG-1 protein