Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3

In recent years an increase of functional CD4+CD25+ regulatory T cells (Treg cells) has been established for patients with solid tumors, acute leukemias, and lymphomas. We have reported an expanded pool of CD4+CD25high Treg cells in patients with chronic lymphat...

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Main Authors: Marc Beyer, Sabine Classen, Elmar Endl, Matthias Kochanek, Martin R. Weihrauch, Svenja Debey-Pascher, Percy A. Knolle, Joachim L. Schultze
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2011/734036
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author Marc Beyer
Sabine Classen
Elmar Endl
Matthias Kochanek
Martin R. Weihrauch
Svenja Debey-Pascher
Percy A. Knolle
Joachim L. Schultze
author_facet Marc Beyer
Sabine Classen
Elmar Endl
Matthias Kochanek
Martin R. Weihrauch
Svenja Debey-Pascher
Percy A. Knolle
Joachim L. Schultze
author_sort Marc Beyer
collection DOAJ
description In recent years an increase of functional CD4+CD25+ regulatory T cells (Treg cells) has been established for patients with solid tumors, acute leukemias, and lymphomas. We have reported an expanded pool of CD4+CD25high Treg cells in patients with chronic lymphatic leukemia (CLL), multiple myeloma (MM) as well as its premalignant precursor monoclonal gammopathy of undetermined significance (MGUS). In healthy individuals, low-level expression of CD127 on T cells in addition to the expression of FOXP3 has been associated with Treg cells. Here, we demonstrate that the expanded FOXP3+ T-cell population in patients with colorectal cancer, CLL, MGUS, MM, follicular lymphoma, and Hodgkin's disease are exclusively CD127low Treg cells and were strongly suppressive. A significant portion of CD127lowFOXP3+ Treg cells expressed only low levels of CD25 suggesting that the previously reported expansion of CD25+ Treg cells underestimates the true expansion. The assessment of CCR7 and CD45RA expression on the expanded CD4+CD127lowFOXP3+ Treg cells revealed an increase of both naïve as well as central and effector memory Treg cells in peripheral blood. Our data strongly support superiority of combined CD127 and FOXP3 analysis in comparison to CD25 and FOXP3 assessment for further quantification of Treg cells in malignant diseases.
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spelling doaj-art-4eaa9cd671a54d299d9c3d93bb65ba842025-02-03T06:07:03ZengWileyClinical and Developmental Immunology1740-25221740-25302011-01-01201110.1155/2011/734036734036Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3Marc Beyer0Sabine Classen1Elmar Endl2Matthias Kochanek3Martin R. Weihrauch4Svenja Debey-Pascher5Percy A. Knolle6Joachim L. Schultze7Laboratory for Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Carl-Troll-Street 31, 53115 Bonn, GermanyLaboratory for Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Carl-Troll-Street 31, 53115 Bonn, GermanyInstitute for Molecular Medicine and Experimental Immunology, University of Bonn,, 53105 Bonn, GermanyClinic I for Internal Medicine, University of Cologne, Kerpenerstr. 62, 50924 Cologn, GermanyClinic I for Internal Medicine, University of Cologne, Kerpenerstr. 62, 50924 Cologn, GermanyLaboratory for Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Carl-Troll-Street 31, 53115 Bonn, GermanyInstitute for Molecular Medicine and Experimental Immunology, University of Bonn,, 53105 Bonn, GermanyClinic I for Internal Medicine, University of Cologne, Kerpenerstr. 62, 50924 Cologn, GermanyIn recent years an increase of functional CD4+CD25+ regulatory T cells (Treg cells) has been established for patients with solid tumors, acute leukemias, and lymphomas. We have reported an expanded pool of CD4+CD25high Treg cells in patients with chronic lymphatic leukemia (CLL), multiple myeloma (MM) as well as its premalignant precursor monoclonal gammopathy of undetermined significance (MGUS). In healthy individuals, low-level expression of CD127 on T cells in addition to the expression of FOXP3 has been associated with Treg cells. Here, we demonstrate that the expanded FOXP3+ T-cell population in patients with colorectal cancer, CLL, MGUS, MM, follicular lymphoma, and Hodgkin's disease are exclusively CD127low Treg cells and were strongly suppressive. A significant portion of CD127lowFOXP3+ Treg cells expressed only low levels of CD25 suggesting that the previously reported expansion of CD25+ Treg cells underestimates the true expansion. The assessment of CCR7 and CD45RA expression on the expanded CD4+CD127lowFOXP3+ Treg cells revealed an increase of both naïve as well as central and effector memory Treg cells in peripheral blood. Our data strongly support superiority of combined CD127 and FOXP3 analysis in comparison to CD25 and FOXP3 assessment for further quantification of Treg cells in malignant diseases.http://dx.doi.org/10.1155/2011/734036
spellingShingle Marc Beyer
Sabine Classen
Elmar Endl
Matthias Kochanek
Martin R. Weihrauch
Svenja Debey-Pascher
Percy A. Knolle
Joachim L. Schultze
Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3
Clinical and Developmental Immunology
title Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3
title_full Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3
title_fullStr Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3
title_full_unstemmed Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3
title_short Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3
title_sort comparative approach to define increased regulatory t cells in different cancer subtypes by combined assessment of cd127 and foxp3
url http://dx.doi.org/10.1155/2011/734036
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