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Peripheral T Lymphocytes Recirculating Back into the Thymus Can Mediate Thymocyte Positive Selection

Jörg Kirberg^1,*, Nabil Bosco^1,, Jean-Christophe Deloulme, Rod Ceredig^, and Fabien Agenès^2,¶,||

^* Max Planck Institute of Immunobiology, Freiburg, Germany; Department of Biomedicine, Developmental and Molecular Immunology Laboratory, University of Basel, Basel, Switzerland; Institut National de la Santé et de la Recherche Médicale Unité 836, Grenoble, France; Institut National de la Santé et de la Recherche Médicale Unité 645, Besancon, France; ^¶ Institut National de la Santé et de la Recherche Médicale ADR Lyon, Lyon, France; and ^|| Institut National de la Santé et de la Recherche Médicale Unité 743, Université de Montréal, CR-CHUM Montreal, Quebec, Canada

The thymus continuously produces T lymphocytes that contribute to the maintenance of the peripheral T cell pool. Since peripheral recirculating T cells represent a very minor population among total thymocytes in normal animals, the relationship between the thymus and secondary lymphoid organs is generally considered unidirectional. Recently, several reports have described the presence of recirculating T cells in the thymus, raising issues regarding their possible function. In this article, we show that the niche for recirculating T cells in the thymus, i.e., their absolute number, is the same in lymphopenic and normal mice. Using a novel combination of TCR-transgenic mice in which the ligand necessary for positive selection of host T cells is only expressed by transferred donor T cells, we show that mature T cells recirculating back to the thymus can mediate positive selection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ J.K. and N.B. contributed equally to this work.

² Address correspondence and reprint requests to Dr. Fabien Agenès, Institut National de la Santé et de la Recherche Médicale Unité 743, 264 Boulevard René-Lévesque Est, Montreal, Quebec H2X 1P1, Canada. E-mail address: fabien.agenes{at}inserm.fr

³ Abbreviations used in this paper: TSP, thymus-settling cell; DP, double positive; LN, lymph node; SP, single positive; tg, transgenic; HA, hemagglutinin; PI, propidium iodide; CK, cytokeratin; WT, wild type; HSA, human stable Ag.

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