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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0802911v1 183/4/2217    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Schmutz, S. Articles by Finke, D. PubMed PubMed Citation Articles by Schmutz, S. Articles by Finke, D. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH

Cutting Edge: IL-7 Regulates the Peripheral Pool of Adult ROR⁺ Lymphoid Tissue Inducer Cells¹

Sandrine Schmutz^*, Nabil Bosco, Stephane Chappaz^*, Onur Boyman, Hans Acha-Orbea, Rhodri Ceredig^¶, Antonius G. Rolink and Daniela Finke^2,*

^* Division of Developmental Immunology and Division of Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland; Division of Immunology and Allergy, University Hospital of Lausanne (Central University Hospital of Vaud), Lausanne, Switzerland; Department of Biochemistry, University of Lausanne, Epalinges, Switzerland; and ^¶ Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, Department of Physiology, National University of Ireland, Galway, Ireland

During fetal life, CD4⁺CD3^– lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer’s patch development in mice. In adult animals, CD4⁺CD3^– cells are found in low numbers in lymphoid organs. Whether adult CD4⁺CD3^– cells are LTi cells and are generated and maintained through cytokine signals has not been directly addressed. In this study we show that adult CD4⁺CD3^– cells adoptively transferred into neonatal CXCR5^–/– mice induced the formation of intestinal lymphoid tissues, demonstrating for the first time their bona fide LTi function. Increasing IL-7 availability in wild-type mice either by IL-7 transgene expression or treatment with IL-7/anti-IL-7 complexes increased adult LTi cell numbers through de novo generation from bone marrow cells and increased the survival and proliferation of LTi cells. Our observations demonstrate that adult CD4⁺lineage^– cells are LTi cells and that the availability of IL-7 determines the size of the adult LTi cell pool.

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 This work was supported by the Swiss National Science Foundation Grant PPOOA-68855, the Gottfried and Julia Bangerter-Rhyner Foundation, and a grant from Swiss Mobiliar (to D. F.). A.R. is holder of the Chair of Immunology endowed by Hoffman-La Roche Ltd., Basel, Switzerland.

² Address correspondence and reprint requests to Prof. Daniela Finke, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland. E-mail address: Daniela.Finke{at}unibas.ch

³ Abbreviations used in this paper: LT, lymphotoxin; BM, bone marrow; E, embryonic day; FL, fetal liver; lin, lineage; ILF, isolated lymphoid follicle; LN, lymph node; LTi, lymphoid tissue inducer; PP, Peyer’s patch; ROR, retinoic acid-related orphan receptor; WT, wild type; H-IL-7, high IL-7.

⁴ The online version of this article contains supplemental material.