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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.
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IMMUNOBIOLOGY
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
From the Department of Molecular Tumor Biology and Tumor Immunology and the Clinic I for Internal Medicine, University of Cologne; the Institute of Immunology, University of Heidelberg; and the Institute for Molecular Medicine and Experimental Immunology, University of Bonn, Germany.
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 premalignant 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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