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.