In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma.
In solid tumors, leukemias, and lymphomas, increased frequencies of functional CD4+CD25(high) regulatory T cells (T(reg) cells) have been previously demonstrated. In healthy individuals, T(reg) 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(+) T(reg) 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 T(reg) cells in both healthy controls and multiple myeloma patients point to peripheral expansion as the prominent mechanism of increased frequencies of naive T(reg) cells in these cancer patients. These findings strongly suggest that the increase of functional T(reg) cells in cancer patients is a response to the process of malignant transformation.
Beyer
Marc
M
Molecular Tumor Biology and Tumor Immunology, Clinic I for Internal Medicine, University of Cologne, Joseph-Stelzmann Strasse 9/Haus 16, 50931 Cologne, Germany.
Kochanek
Matthias
M
Giese
Thomas
T
Endl
Elmar
E
Weihrauch
Martin R
MR
Knolle
Percy A
PA
Classen
Sabine
S
Schultze
Joachim L
JL
D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood* / Q000235:genetics / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood / Q000235:genetics; D009101:Multiple Myeloma / Q000097:blood* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000097:blood / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000097:blood / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000097:blood*
D015703:Antigens, CD; C515370:CCR7 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011948:Receptors, Antigen, T-Cell; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens