Expression of a CD3 epsilon transgene in CD3 epsilon(null) mice does not restore CD3 gamma and delta expression but efficiently rescues T cell development from a subpopulation of prothymocytes.

The TCR-associated CD3 complex consists of four subunits, i.e. CD3g, d, e and ζ, which are expressed very early in T cell development prior to the expression of the TCR and the pre-TCR a chain. It is unclear whether the expression of each CD3 protein is independent of, or is influenced by, other CD3 subunits. To study whether CD3e regulates expression of CD3g and d genes, we generated a strain of CD3e-deficient mice termed CD3e ΔP/ΔP (e ΔP ), in which the promoter of CD3e was disrupted, and subsequently reconstituted these mice with a CD3e transgene. In the e ΔP mice, T cell development is arrested at the double-negative stage and targeting the CD3e gene caused severe inhibition of CD3g and d gene expression. Introduction of the CD3e transgene did not restore CD3g and d expression. However, a very small fraction of prothymocytes that expressed CD3g and d was rescued upon reconstitution of the CD3e transgene. Remarkably, this rescue led to a very efficient differentiation and maturation of thymocytes, resulting in a significant T cell population in the periphery. These results demonstrate that CD3e does not regulate expression of CD3g and d genes, and underscore the capacity of each prothymocyte to give rise to a large number of mature peripheral T cells.