Negative selection of precursor thymocytes before their differentiation into CD4+CD8+ cells.

Thymic selection of the developing T cell repertoire is thought to occur at the CD4+CD8+ stage of differentiation and to be determined by the specificity of the T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals can inhibit the differentiation of precursor thymocytes into CD4+CD8+ cells, which suggests that selection might occur earlier than thought. Indeed, in a negatively selecting male thymus, CD4-CD8lo precursor thymocytes that express a transgenic TCR to male antigen are developmentally arrested as a consequence of antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur before the CD4+CD8+ stage of differentiation.

[1]  S. Hedrick,et al.  In vivo and in vitro clonal deletion of double-positive thymocytes , 1992, The Journal of experimental medicine.

[2]  W. Swat,et al.  Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen-presenting cells , 1991, Nature.

[3]  B. Rocha,et al.  Peripheral selection of the T cell repertoire. , 1991, Science.

[4]  A. Heimberger,et al.  Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. , 1990, Science.

[5]  D. Longo,et al.  Peripheral clonal elimination of functional T cells. , 1990, Science.

[6]  H. Petrie,et al.  Lineage relationships and developmental kinetics of immature thymocytes: CD3, CD4, and CD8 acquisition in vivo and in vitro , 1990, The Journal of experimental medicine.

[7]  H. Macdonald,et al.  Programmed death of autoreactive thymocytes , 1990, Nature.

[8]  H. Pircher,et al.  Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen , 1989, Nature.

[9]  L. Lefrançois,et al.  Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function , 1989, The Journal of experimental medicine.

[10]  M. Moore,et al.  T cell receptor expression on immature thymocytes with in vivo and in vitro precursor potential , 1989, European journal of immunology.

[11]  Christophe Benoist,et al.  Positive selection of the T cell repertoire: Where and when does it occur? , 1989, Cell.

[12]  Mark M. Davis,et al.  Antigen/MHC-specific T cells are preferentially exported from the thymus in the presence of their MHC ligand , 1989, Cell.

[13]  Mark M. Davis,et al.  Phenotypic differences between αβ versus β T-cell receptor transgenic mice undergoing negative selection , 1989, Nature.

[14]  P. Marrack,et al.  Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. , 1989, Journal of immunology.

[15]  T. Hünig.  Cross‐linking of the T cell antigen receptor interferes with the generation of CD4+8+ thymocytes from their immediate CD4−8+ precursors , 1988, European journal of immunology.

[16]  David M. Kranz,et al.  Positive and negative selection of an antigen receptor on T cells in transgenic mice , 1988, Nature.

[17]  Y. Uematsu,et al.  Thymic major histocompatibility complex antigens and the αβ T-cell receptor determine the CD4/CD8 phenotype of T cells , 1988, Nature.

[18]  R. Schwartz,et al.  Deletion of self-reactive thymocytes occurs at a CD4+8+ precursor stage , 1988, Nature.

[19]  M. Egerton,et al.  Immature CD4- CD8+ murine thymocytes. , 1988, Cellular immunology.

[20]  H. Macdonald,et al.  A cd3− subset of cd4−8+ thymocytes: a rapidly cycling intermediate in the generation of cd4+8+ cells , 1988, European journal of immunology.

[21]  D. Paterson,et al.  An intermediate cell in thymocyte differentiation that expresses CD8 but not CD4 antigen , 1987, The Journal of experimental medicine.

[22]  P. Marrack,et al.  T cell tolerance by clonal elimination in the thymus , 1987, Cell.

[23]  J. Bluestone,et al.  Identification of a monoclonal antibody specific for a murine T3 polypeptide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[24]  C. Dani,et al.  Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. , 1985, Nucleic acids research.

[25]  J. Lowenthal,et al.  Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells , 1985, Nature.

[26]  H. Boehmer,et al.  Developmental biology of T cells in T cell-receptor transgenic mice. , 1990 .

[27]  D. Pardoll,et al.  Molecular and cellular events of T cell development. , 1989, Advances in immunology.

[28]  S. N. Gettner,et al.  Unusual intron in the immunoglobulin domain of the newly isolated murine CD4 (L3T4) gene , 1987, Nature.