Restoration of T Cell Development in RAG-2-Deficient Mice by Functional TCR Transgenes

Abstract

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 CD3γδε and ζ proteins intracellularly. Introduction of a TCRβ transgene, but not a TCRα transgene, into the RAG-2 -/- background 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 CD3γδε 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.