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Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2001, Vol. 97, No. 5, pp. 1336-1342 IMMUNOBIOLOGY Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells Myriam Capone, Paola Romagnoli, Friedrich Beermann, H. Robson MacDonald, and Joost P. M. van Meerwijk From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; the Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; the Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland; and the Faculty of Life Sciences (UFR-SVT), University Toulouse III, Toulouse, France. Thymic positive and negative selection of developing T lymphocytes confronts us with a paradox: How can a T-cell antigen receptor (TCR)-major histocompatibility complex (MHC)/peptide interaction in the former process lead to transduction of signals allowing for cell survival and in the latter induce programmed cell death or a hyporesponsive state known as anergy? One of the hypotheses put forward states that the outcome of a TCR-MHC/peptide interaction depends on the cell type presenting the selecting ligand to the developing thymocyte. Here we describe the development and lack of self-tolerance of CD8+ T lymphocytes in transgenic mice expressing MHC class I molecules in the thymus exclusively on cortical epithelial cells. Despite the absence of MHC class I expression on professional antigen-presenting cells, normal numbers of CD8+ cells were observed in the periphery. Upon specific activation, transgenic CD8+ T cells efficiently lysed syngeneic MHC class I+ targets in vitro and in vivo, indicating that thymic cortical epithelium (in contrast to medullary epithelium and antigen-presenting cells of hematopoietic origin) is incapable of tolerance induction. Thus, compartmentalization of the antigen-presenting cells involved in thymic positive selection and tolerance induction can (at least in part) explain the positive/negative selection paradox. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. M. McCaughtry, T. A. Baldwin, M. S. Wilken, and K. A. Hogquist Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla J. Exp. Med., October 27, 2008; 205(11): 2575 - 2584. [Abstract] [Full Text] [PDF] J. Ribot, G. Enault, S. Pilipenko, A. Huchenq, M. Calise, D. Hudrisier, P. Romagnoli, and J. P. 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