In the absence of thymopoiesis, T lymphocytes are nevertheless present, mainly in the gut epithelium. Ontogeny of the extrathymic pathway and the extent of its involvement in euthymic mice are controversial. These questions have been addressed by assessing the expression of recombinase activating gene (RAG) through the use of green fluorescent protein RAG2 transgenic mouse models. In athymic mice, T lymphopoiesis occurs mainly in the mesenteric lymph node and less in the Peyer's patches. Ontogenic steps of this lymphopoiesis resemble those of thymopoiesis, but with an apparent bias toward γδ T cell production and with a paucity of oligoclonal αβ T cells possibly resulting from a deficit in positive selection. Whether in athymic or euthymic mice, neither T intraepithelial lymphocytes (IEL) nor cryptopatch cells (reported to contain precursors of IEL) displayed fluorescence indicating recent RAG protein synthesis. Newly made T cells migrate from the mesenteric node into the thoracic duct lymph to reach the gut mucosa. In euthymic mice, this extrathymic pathway is totally repressed, except in conditions of severe lymphocytic depletion. Thus, in normal animals, all gut T IEL, including CD8αα+ cells, are of thymic origin, CD8αα+ TCRαβ+ IEL being the likely progeny of double negative NK1-1− thymocytes, which show polyclonal Vα and Vβ repertoires.
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3 February 2003
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January 27 2003
Extrathymic T Cell Lymphopoiesis : Ontogeny and Contribution to Gut Intraepithelial Lymphocytes in Athymic and Euthymic Mice
Delphine Guy-Grand,
Delphine Guy-Grand
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
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Orly Azogui,
Orly Azogui
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
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Susanna Celli,
Susanna Celli
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
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Sylvie Darche,
Sylvie Darche
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
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Michel C. Nussenzweig,
Michel C. Nussenzweig
2Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
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Philippe Kourilsky,
Philippe Kourilsky
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
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Pierre Vassalli
Pierre Vassalli
3Département de Pathologie, Centre Médical Universitaire, CH-1211, Genève 4, Switzerland
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Delphine Guy-Grand
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
Orly Azogui
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
Susanna Celli
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
Sylvie Darche
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
Michel C. Nussenzweig
2Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
Philippe Kourilsky
1Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 75724 Paris Cedex 15, France
Pierre Vassalli
3Département de Pathologie, Centre Médical Universitaire, CH-1211, Genève 4, Switzerland
Address correspondence to Delphine Guy-Grand, Unité de Biologie Moléculaire du Gène, INSERM U277 and Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33-1-40-61-32-09; Fax: 33-1-45-68-85-48; E-mail: [email protected]; or Pierre Vassalli, Département de Pathologie, Centre Médical Universitaire, 1 rue Michel Servet, CH-1211, Genève 4, Switzerland. Phone: 41-22-347-56-30; Fax: 41-22-347-56-41; E-mail: [email protected]
The online version of this article contains supplemental material.
*
Abbreviations used in this paper: DN, double negative; DP, double positive; GFP, green fluorescent protein; IEL, intraepithelial lymphocytes; LP, lamina propria; MLN, mesenteric lymph node; PP, Peyer's patches; SP, single positive; Tg, transgenic; TN, triple negative; Tx, thymectomized.
Received:
September 17 2002
Revision Received:
December 17 2002
Accepted:
December 17 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (3): 333–341.
Article history
Received:
September 17 2002
Revision Received:
December 17 2002
Accepted:
December 17 2002
Citation
Delphine Guy-Grand, Orly Azogui, Susanna Celli, Sylvie Darche, Michel C. Nussenzweig, Philippe Kourilsky, Pierre Vassalli; Extrathymic T Cell Lymphopoiesis : Ontogeny and Contribution to Gut Intraepithelial Lymphocytes in Athymic and Euthymic Mice . J Exp Med 3 February 2003; 197 (3): 333–341. doi: https://doi.org/10.1084/jem.20021639
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