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

• DOI: 10.1126/science.8430336
• Publication Date: 2006-10-05T23:05:09Z
• Authors: Yoichi Shinkai; Shigeo Koyasu; Kei-ichi Nakayama; Kenneth M. Murphy; Dennis Y. Loh; Ellis L. Reinherz; Frederick W. Alt
• Keywords: Base Sequence; CD3 Complex; CD8 Antigens; Receptors, Antigen, T-Cell, alpha-beta; Cell Membrane; Molecular Sequence Data; Antibodies, Monoclonal; Gene Expression; Proteins; Mice, Transgenic; Receptors, Antigen, T-Cell, gamma-delta; Polymerase Chain Reaction; DNA-Binding Proteins; Molecular Weight; Mice; 03 medical and health sciences; 0302 clinical medicine; Oligodeoxyribonucleotides; T-Lymphocyte Subsets; CD4 Antigens; Animals; Electrophoresis, Polyacrylamide Gel

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.