T cell development in mice lacking the CD3-zeta/eta gene.
The CD3-zeta and CD3-eta polypeptides are two of the components of the T cell antigen receptor (TCR) which contribute to its efficient cell surface expression and account for part of its transducing capability. CD3-zeta and CD3-eta result from the alternative splicing of a single gene designated CD3-zeta/eta. To evaluate the role of these subunits during T cell development, we have produced mice with a disrupted CD3-zeta/eta gene. The analysis of thymocyte populations from the CD3-zeta/eta-/- homozygous mutant mice revealed that they have a profound reduction in the surface levels of TCR complexes and that the products of the CD3-zeta/eta gene appear to be needed for the efficient generation and/or survival of CD4+CD8+ thymocytes. Despite the almost total absence of mature single positive thymocytes, the lymph nodes from zeta/eta-/- mice were found to contain unusual CD4+CD8- and CD4-CD8+ single positive cells which were CD3-. In contrast to the situation observed in the thymus, the thymus-independent gut intraepithelial lymphocytes present in zeta/eta-/- mice do express TCR complexes on their surface and these are associated with Fc epsilon RI gamma homodimers. These results establish an essential role for the CD3-zeta/eta gene products during intrathymic T cell differentiation and further emphasize the difference between conventional T cells and thymus-independent gut intraepithelial lymphocytes.
Malissen
M
M
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Gillet
A
A
Rocha
B
B
Trucy
J
J
Vivier
E
E
Boyer
C
C
Köntgen
F
F
Brun
N
N
Mazza
G
G
Spanopoulou
E
E
D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000235:genetics*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002999:Clone Cells; D017353:Gene Deletion; D007422:Intestines / Q000166:cytology / Q000196:embryology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000196:embryology / Q000276:immunology; D046911:Macromolecular Substances; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2