Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes

Introduction of TCRα transgene, TCRβ transgene, or both into RAG-2^-/- mice differentially rescues T cell development. RAG-2 ^-/- mice have small numbers of TCR^-CD4^-CD8 ^- (double negative, DN) thymocytes that express CD3γδ ∈ and ζ proteins intracellularly. Introduction of a TCRβ transgene, but not a TCRα transgene, into the RAG-2^-/- back-ground restored normal numbers of thymocytes. These cells were CD4 ⁺CD8⁺ (double positive, DP) and expressed small amounts of surface TCRβ chain dimers in association with CD3γδ∈ but not ζ. RAG-2^-/- mice that expressed α and β TCR transgenes developed both DP and single positive thymocytes. Thus, the TCRβ subunit, possibly in association with a novel CD3 complex, participates in the DN to the DP transition.