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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3940-3949. Prepublished online as a Blood First Edition Paper on January 12, 2006; DOI 10.1182/blood-2005-09-3671. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-09-3671v1 107/10/3940    most recent e-Letter: Submit a Response Alert me when this article is cited Alert me when e-Letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Beyer, M. Articles by Schultze, J. L Search for Related Content PubMed PubMed Citation Articles by Beyer, M. Articles by Schultze, J. L Social Bookmarking                         What's this?  Previous Article  |  Next Article  Submitted September 13, 2005 Accepted January 4, 2006 In vivo peripheral expansion of naive CD4+CD25high FOXP3+ regulatory T cells in patients with multiple myeloma Marc Beyer, Matthias Kochanek, Thomas Giese, Elmar Endl, Martin R Weihrauch, Percy A Knolle, Sabine Classen, and Joachim L Schultze* Molecular Tumor Biology and Tumor Immunology, University of Cologne, Cologne, Germany; Clinic I for Internal Medicine, University of Cologne, Cologne, Germany Institute of Immunology, University of Heidelberg, Heidelberg, Germany Institute for Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany * Corresponding author; email: joachim.schultze{at}uk-koeln.de. In solid tumors, leukemias, and lymphomas, increased frequencies of functional CD4+CD25high regulatory T cells (Treg cells) have been previously demonstrated. In healthy individuals, Treg cells consist not only of memory but also of naive T cells, which can undergo peripheral expansion and are characterized by a relative enrichment for autoreactive T cell receptors. Here we demonstrate in patients with pre-malignant monoclonal gammopathy of undetermined significance and patients with multiple myeloma that functional FOXP3+ Treg cells of naive, central and effector memory phenotype as determined by CCR7 and CD45RA expression are significantly expanded. Low frequencies of T cell receptor excision circles in naive Treg cells in both healthy controls and multiple myeloma patients point to peripheral expansion as the prominent mechanism of increased frequencies of naive Treg cells in these cancer patients. These findings strongly suggest that the increase of functional Treg cells in cancer patients is a response to the process of malignant transformation. 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