Expression of a CD3ε transgene in CD3ε(null) mice does not restore CD3γ and δ expression but efficiently rescues T cell development from a subpopulation of prothymocytes

Abstract

The TCR-associated CD3 complex consists of four subunits, i.e. CD3γ, δ, ε and ζ, which are expressed very early in T cell development prior to the expression of the TCR and the pre-TCR α chain. It is unclear whether the expression of each CD3 protein is independent of, or is influenced by, other CD3 subunits. To study whether CD3ε regulates expression of CD3γ and δ genes, we generated a strain of CD3ε-deficient mice termed CD3εΔP/ΔP (ε(ΔP)), in which the promoter of CD3ε was disrupted, and subsequently reconstituted these mice with a CD3ε transgene. In the ε(ΔP) mice, T cell development is arrested at the double-negative stage and targeting the CD3ε gene caused severe inhibition of CD3γ and δ gene expression. Introduction of the CD3ε transgene did not restore CD3γ and δ expression. However, a very small fraction of prothymocytes that expressed CD3γ and δ was rescued upon reconstitution of the CD3ε 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 CD3ε does not regulate expression of CD3γ and δ genes, and underscore the capacity of each prothymocyte to give rise to a large number of mature peripheral T cells.