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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901334v1 183/6/3574    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 Casetti, R. Articles by Malkovsky, M. PubMed PubMed Citation Articles by Casetti, R. Articles by Malkovsky, M.

Cutting Edge: TGF-β1 and IL-15 Induce FOXP3⁺ Regulatory T Cells in the Presence of Antigen Stimulation¹

Rita Casetti^2,*, Chiara Agrati^*, Marianne Wallace, Alessandra Sacchi^*, Federico Martini^*, Angelo Martino^*, Alessandra Rinaldi^* and Miroslav Malkovsky

^* Laboratory of Cellular Immunology, National Institute for Infectious Diseases "Lazzaro Spallanzani" Instituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy; and Department of Medical Microbiology and Immunology and University of Wisconsin Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792

Several subsets of β regulatory T cells (Tregs) have been described and studied intensively, but the potential regulatory role of T cells remains largely unclear. Lymphocytes expressing TCR are involved in both innate and adaptive immune responses, and their major adult human peripheral blood subset (V9V2) displays a broad reactivity against microbial agents and tumors. In this study we report that T lymphocytes with regulatory functions (V2 Tregs) are induced in vitro in the presence of specific Ag stimulation and cytokines (TGF-β1 and IL-15). These cells express FOXP3 and, similarly as β Tregs, suppress the proliferation of anti-CD3/anti-CD28 stimulated-PBMC. Phenotypic and functional analyses of V2 Tregs will very likely improve our understanding about the role of T cells in the pathogenesis of autoimmune, infectious, and neoplastic diseases.

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 study was supported by grants from the National Institutes of Health, U. S. Department of Defense, and the Italian Ministry of Health.

² Address correspondence and reprint requests to Dr. Rita Casetti, Laboratory of Cellular Immunology, National Institute for Infectious Diseases "Lazzaro Spallanzani" Instituto di Ricovero e Cura a Carattere Scientifico, Via Portuense 292, 00149 Rome, Italy. E-mail address: casetti{at}inmi.it

³ Abbreviations used in this paper: Treg, regulatory T cell; CFDA-SE, carboxyfluorescein diacetate succinimidyl ester; FOXP3, Forkhead box P3; IPP, isopentenyl pyrophosphate.