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Thymic heterotypic cellular complexes in gene-targeted mice with defined blocks in T cell development and adhesion molecule expression

1998; Wiley; Volume: 28; Issue: 9 Linguagem: Inglês

10.1002/(sici)1521-4141(199809)28

1521-4141

Antonio Oliveira-dos-Santos, Josef Penninger, Theresa Rieker–Geley, Goichi Matsumoto, Tak M. Mak, Georg Wick,

Immune Cell Function and Interaction

European Journal of ImmunologyVolume 28, Issue 9 p. 2882-2892 ArticleFree Access Thymic heterotypic cellular complexes in gene-targeted mice with defined blocks in T cell development and adhesion molecule expression Antonio J. Oliveira-dos-Santos, Antonio J. Oliveira-dos-Santos Institute for General and Experimental Pathology Medical School, University of Innsbruck, Innsbruck, AustriaSearch for more papers by this authorJosef M. Penninger, Josef M. Penninger Amgen Institute and Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, CanadaSearch for more papers by this authorTheresa Rieker-Geley, Theresa Rieker-Geley Institute for General and Experimental Pathology Medical School, University of Innsbruck, Innsbruck, AustriaSearch for more papers by this authorGoichi Matsumoto, Goichi Matsumoto Amgen Institute and Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, CanadaSearch for more papers by this authorTak M. Mak, Tak M. Mak Amgen Institute and Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, CanadaSearch for more papers by this authorGeorg Wick, Georg Wick Institute for General and Experimental Pathology Medical School, University of Innsbruck, Innsbruck, AustriaSearch for more papers by this author Antonio J. Oliveira-dos-Santos, Antonio J. Oliveira-dos-Santos Institute for General and Experimental Pathology Medical School, University of Innsbruck, Innsbruck, AustriaSearch for more papers by this authorJosef M. Penninger, Josef M. Penninger Amgen Institute and Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, CanadaSearch for more papers by this authorTheresa Rieker-Geley, Theresa Rieker-Geley Institute for General and Experimental Pathology Medical School, University of Innsbruck, Innsbruck, AustriaSearch for more papers by this authorGoichi Matsumoto, Goichi Matsumoto Amgen Institute and Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, CanadaSearch for more papers by this authorTak M. Mak, Tak M. Mak Amgen Institute and Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, CanadaSearch for more papers by this authorGeorg Wick, Georg Wick Institute for General and Experimental Pathology Medical School, University of Innsbruck, Innsbruck, AustriaSearch for more papers by this author First published: 28 March 2006 https://doi.org/10.1002/(SICI)1521-4141(199809)28:09 3.0.CO;2-1Citations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Thymocytes form unique multicellular complexes with epithelial cells (thymic nurse cells, TNC) and rosettes (ROS) with macrophages, epithelial cells and dendritic cells. To investigate the role of differentiation checkpoints in the formation of the thymic heterotypic complexes in vivo, we used mutant mice which have genetically defined blocks at early and late stages of T cell development. We show that RAG-1−/−, TCRβ−/−, and p56lck−/− mice lack thymocyte ROS formation with epithelial cells, macrophages, or dendritic cells. TNC formation was not affected by TCRβ and p56lck gene mutations but partially decreased in RAG-1−/− mice, indicating that TNC are the earliest thymocyte-stromal cell complexes formed in development, whereas ROS only appear after thymocytes have rearranged and expressed a functional TCRβ chain. Genetic blocks in CD8 lineage commitment (CD8−/− and IFN regulatory factor-1−/− mice) and positive and negative T cell selection (CD45−/−, TCRα−/−, and CD30−/− mice) did not affect thymocyte-stromal cell complexes. Surprisingly, CD4−/− mice, but not MHC class II−/− mice, had significantly reduced numbers of TNC and ROS, in particular, a severe defect in ROS formation with thymic dendritic cells. The CD4−/− block in ROS and TNC formation was rescued by the introduction of a human CD4 transgene. Moreover, we show that the adhesion receptors CD44 and LFA-1 cooperate in the formation of the thymic microenvironment. These results provide genetic evidence on the role of defined stages in T cell development and adhesion molecules on thymocyte/stromal cell interactions in vitro. References 1 Boyd, R. L., Tucek, C. L., Godfrey, D. I., Izon, D. J., Wilson, T. J., Davidson, N. J., Bean, A. G., Ladyman, H. M., Ritter, M. A. and Hugo, P., The thymic microenvironment. Immunol. 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