The Journal of Experimental Medicine
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Published 2 September 2003. doi:10.1084/jem.20030794
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© Rockefeller University Press, 0022-1007/2003/9/757 $5.00
The Journal of Experimental Medicine, Volume 198, Number 5, 757-769

Thymic Medullary Epithelial Cell Differentiation, Thymocyte Emigration, and the Control of Autoimmunity Require Lympho–Epithelial Cross Talk via LTßR

Thomas Boehm1, Stefanie Scheu2, Klaus Pfeffer2 and Conrad C. Bleul1

1 Max Planck Institute for Immunobiology, 79108 Freiburg, Germany
2 Institute of Medical Microbiology, Heinrich-Heine-Universität, Düsseldorf, 40225 Düsseldorf, Germany

Address correspondence to Conrad C. Bleul, Max Planck Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany. Phone: 49-761-5108-364; Fax: 49-761-5108-333; email: bleul{at}immunbio.mpg.de

Thymocytes depend on the interaction with thymic epithelial cells for the generation of a diverse, nonautoreactive T cell repertoire. In turn, thymic epithelial cells acquire their three-dimensional cellular organization via instructive signals from developing thymocytes. The nature of these signals has been elusive so far. We show that thymocytes and medullary epithelial cells (MECs) communicate via the lymphotoxin ß receptor (LTßR) signaling axis. Normal differentiation of thymic MECs requires LTßR ligand on thymocytes and LTßR together with nuclear factor–{kappa}B-inducing kinase (Nik) in thymic epithelial cells. Impaired lympho–epithelial cross talk in the absence of the LTßR causes aberrant differentiation and reduced numbers of thymic MECs, leads to the retention of mature T lymphocytes, and is associated with autoimmune phenomena, suggesting an unexpected role for LTßR signaling in central tolerance induction.

Key Words: thymus • thymopoiesis • development • epithelial cells • selection


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