Precommitment of CD4+CD8+Thymocytes to Either CD4 or CD8 Lineages

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 19; pp. 8982 - 8986
• Main Authors: Crompton, T, Lees, R K, Pircher, H, MacDonald, H R
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.10.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Aging - immunology; Animals; Antibodies; Antibodies, Monoclonal; Biological and medical sciences; CD4 Antigens - analysis; CD4 Antigens - immunology; CD8 Antigens - analysis; CD8 Antigens - immunology; Cell Cycle; Cellular biology; Crosses, Genetic; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Homeodomain Proteins; Immunity (Disease); Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Male; Medical research; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Molecules; Positive selection; Protein Biosynthesis; Proteins - genetics; Receptors, Antigen, T-Cell, alpha-beta - genetics; RNA, Messenger - analysis; Stochastic models; T cell antigen receptors; T lymphocytes; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymocytes; Transgenes; Transgenic animals; T cell receptor; Thymus gland; Thymocyte; Major histocompatibility system; Selection; Rodentia; Class II histocompatibility antigen; Cell subpopulation; Mechanism; Vertebrata; Mammalia; Mouse; Development; Immunologic repertoire; Class I histocompatibility antigen
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.19.8982

CD4+and CD8+mature T cells arise from CD4+CD8+precursors in the thymus. During this process, cells expressing T-cell receptors (TCRs) reactive with self major histocompatibility complex (MHC) class I or II molecules are positively selected to the CD8 or CD4 lineage, respectively. It is controversial whether lineage commitment of CD4+CD8+thymocytes is controlled directly by TCR specificity for MHC (instructional model) or, alternatively, by processes that operate independently of TCR specificity (stochastic model). We show here that CD4+CD8+thymocytes bearing a MHC class I-restricted transgenic TCR can be subject to two alternative developmental fates. One population of CD4+CD8+cells is positively selected by MHC class I molecules to the CD8 lineage as expected, whereas the other CD4+CD8+population rearranges endogenous TCR genes and is positively selected by MHC class II molecules to the CD4 lineage. Blocking TCR-MHC class II interactions in vivo does not interfere with the generation of CD4+CD8+cells expressing endogenous TCRs but does prevent their subsequent maturation to CD4+cells. These data support a version of the stochastic model in which CD4+CD8+thymocytes are precommitted to the CD4 or CD8 lineage independently of TCR specificity for MHC and prior to positive selection.