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Development of CD4⁺ Macrophages from Intrathymic T Cell Progenitors Is Induced by Thymic Epithelial Cells¹

Eiji Esashi^*, Hiroaki Ito^*, Katsuhiko Ishihara, Toshio Hirano^,, Shigeo Koyasu^,¶ and Atsushi Miyajima^2,*,¶

^* Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan; Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences; Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Japan; Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; and ^¶ Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Japan

It was recently demonstrated that there are CD4⁺ macrophages, which exhibit strong phagocytic activity, in the thymus. They are suggested to play an important role for the elimination of apoptotic thymocytes. However, the origin and nature of CD4⁺ macrophages in the thymus remain unexplored. In this study, we describe that the most immature intrathymic progenitors (CD25^–/CD44⁺/FcR⁺) give rise to CD4⁺ macrophages by oncostatin M-responsive thymic epithelial cells (ORTEC) in an IL-7-dependent manner. Neither conditioned medium of ORTEC nor a mixture of cytokines induced CD4⁺ macrophages, and oncostatin M receptor was not expressed in thymocytes, suggesting that the development of CD4⁺ macrophages from the immature thymocytes requires a direct interaction with ORTEC. These results collectively suggest that the development of CD4⁺ macrophages from the intrathymic T cell progenitors is induced by thymic epithelial cells.

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