1. The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells.
- Author
-
Itano, A, Salmon, P, Kioussis, D, Tolaini, M, Corbella, P, and Robey, E
- Subjects
Stem Cell Research - Nonembryonic - Non-Human ,Stem Cell Research ,Underpinning research ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Aetiology ,Inflammatory and immune system ,Animals ,Base Sequence ,CD4 Antigens ,CD4-Positive T-Lymphocytes ,CD8 Antigens ,CD8-Positive T-Lymphocytes ,Cell Differentiation ,Flow Cytometry ,Histocompatibility Antigens Class I ,Lymph Nodes ,Major Histocompatibility Complex ,Mice ,Mice ,Transgenic ,Molecular Sequence Data ,Mutagenesis ,Site-Directed ,Oligodeoxyribonucleotides ,Protein Multimerization ,Receptors ,Antigen ,T-Cell ,Recombinant Proteins ,Signal Transduction ,T-Lymphocyte Subsets ,Thymus Gland ,Medical and Health Sciences ,Immunology - Abstract
Thymocytes must bind major histocompatibility complex (MHC) proteins on thymic epithelial cells in order to mature into either CD8+ cytotoxic T cells or CD4+ helper T cells. Thymic precursors express both CD8 and CD4, and it has been suggested that the intracellular signals generated by CD8 or CD4 binding to class I or II MHC, respectively, might influence the fate of uncommitted cells. Here we test the notion that intracellular signaling by CD4 directs the development of thymocytes to a CD4 lineage. A hybrid protein consisting of the CD8 extracellular and transmembrane domains and the cytoplasmic domain of CD4 (CD884) should bind class I MHC but deliver a CD4 intracellular signal. We find that expression of a hybrid CD884 protein in thymocytes of transgenic mice leads to the development of large numbers of class I MHC-specific, CD4 lineage T cells. We discuss these results in terms of current models for CD4 and CD8 lineage commitment.
- Published
- 1996