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Identification of an IL-7-Dependent Pre-T Committed Population in the Spleen¹

Laetitia Gautreau^*, Marie-Laure Arcangeli^*, Valérie Pasqualetto^*, Anne-Marie Joret^*, Corinne Garcia-Cordier, Jérôme Mégret, Elke Schneider and Sophie Ezine^2,*

^* Institut National de la Santé et de la Recherche Médicale, U591, Paris, France; Université Paris Descartes, Institut Fédératif de Recherche 94 Necker-Enfants Malades; and Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147, Hôpital Necker, Paris, France

Several extrathymic T cell progenitors have been described but their various contributions to the T cell lineage puzzle are unclear. In this study, we provide evidence for a splenic Lin^–Thy1.2⁺ T cell-committed population, rare in B6 mice, abundant in TCR^–/–, CD3^–/–, and nude mice, and absent in IL-7- and Rag-2-deficient mice. Neither B nor myeloid cells are generated in vivo and in vitro. The incidence of these pre-T cells is under the control of thymus and/or mature T cells, as revealed by graft experiments. Indeed, IL-7 consumption by mature T cells inhibits the growth of these pre-T cells. Moreover, the nude spleen contains an additional Lin^–Thy1.2⁺CD25⁺ subset which is detected in B6 mice only after thymectomy. We establish that the full pre-T cell potential and proliferation capacity are only present in the c-kit^low fraction of progenitors. We also show that most CCR9⁺ progenitors are retained in the spleen of nude mice, but present in the blood of B6 mice. Thus, our data describe a new T cell lineage restricted subset that accumulates in the spleen before migration to the thymus.

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 L.G. and M.-L.A. were supported by the Ministère de la Recherche et de la Technologie and by the Association de la Recherche sur le Cancer. This project was supported by the Institut National de la Santé et de la Recherche Médicale, Association de la Recherche sur le Cancer and the Action Concertée Thématique sur les Cellules Souches Adultes (sponsored by the Institut National de la Santé et de la Recherche Médicale, Association Française des Myopathies, Vaincre la Mucoviscidose, Juvenil Diabetes Research Foundation, Ministère de la Jeunesse, de l’Education et de la Recherche) to S.E.

² Address correspondence and reprint requests to Dr. Sophie Ezine, Institut National de la Santé et de la Recherche Médicale U591, Institut Necker, Université Paris V, 156 rue de Vaugirard, Paris, France. E-mail address: ezine{at}necker.fr

³ Abbreviations used in this paper: BM, bone marrow; DN, double negative; i.t., intrathymic(cally); wt, wild type; LSK, Lin^–Sca-1⁺ c-kit⁺; CLP, common lymphoid progenitor; ETP, earliest T cell progenitor; CTP, committed T cell population; IEL, intraepithelial lymphocyte; Tx, thymectomized; LN, lymph nodes; TN, triple negative; DP, double positive.