Functional regulatory T cells are collected in stem cell autografts by mobilization with high-dose cyclophosphamide and granulocyte colony-stimulating factor

被引:51
作者
Condomines, Maud
Quittet, Philippe
Lu, Zhao-Yang
Nadal, Laure
Latry, Pascal
Lopez, Ernesto
Baudard, Marion
Requirand, Guilhem
Duperray, Christophe
Schved, Jean-Francois
Rossi, Jean-Francois
Tarte, Karin
Klein, Bernard
机构
[1] INSERM, U475, F-34197 Montpellier, France
[2] CHU Montpellier, Inst Res Biotherapy, Montpellier, France
[3] Univ Montpellier I, Montpellier, France
[4] CHU Montpellier, Dept Hematol & Clin Oncol, Montpellier, France
[5] CHU Montpellier, Unit Cellular Therapy, Montpellier, France
关键词
D O I
10.4049/jimmunol.176.11.6631
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
High-dose cyclophosphamide (Cy) and G-CSF are widely used to mobilize hemopoietic stem cells for treating patients with high-dose chemotherapy and autologous stem cell transplantation (ASCT). Because lymphocyte count in the graft collected after Cy-G-CSF treatment is an independent survival factor after ASCT for patients with multiple myeloma, our purpose was to study how Cy-G-CSF treatment affects the phenotype and function of T cells in patients with multiple myeloma. Cy induced a 3-fold decrease of T cell counts with a slow and partial T cell recovery of one-third at the time of hemopoietic stem cell collection. Cy-G-CSF treatment did not affect the relative ratios of central memory, effector memory, and late effector CD4(+) or CD8(+) T cells, but a decrease in the percentage of naive CD4(+) cells was observed. The percentages of CD25(+) cells increased 2- to 3-fold in CD4(+) and CD8(+) T cells, the former including both activated CD25(low) and CD25(high) cells. CD4(+)CD25(high) cells were regulatory T cells (Treg) that expressed high levels of FOXP3, CTLA-4, and GITR and displayed in vitro suppressive properties. The recovery of Treg absolute counts after Cy-G-CSF treatment was higher than the recovery of other lymphocyte subpopulations. In conclusion, Cy-G-CSF treatment induces a severe T cell count decrease without deleting Treg, which are potent inhibitors of antitumor response. The present data encourage novel therapeutic strategies to improve T cell recovery following ASCT while limiting Treg expansion.
引用
收藏
页码:6631 / 6639
页数:9
相关论文
共 56 条
[1]   Changes in CD4+ T-Cell Differentiation Phenotype During Structured Treatment Interruption in Patients With Chronic HIV-1 Infection [J].
Alexander, Thomas H. ;
Ortiz, Gabriel M. ;
Wellons, Melissa F. ;
Allen, Andrew ;
Grace, Edward J., II ;
Schweighardt, Becky ;
Brancato, Jason ;
Sandberg, Johan K. ;
Furlan, Scott N. ;
Miralles, G. Diego ;
Nixon, Douglas F. ;
Bartlett, John A. .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2003, 34 (05) :475-481
[2]   IL-7 and IL-15:: therapeutic cytokines for immunodeficiency [J].
Alpdogan, Ö ;
van den Brink, MRM .
TRENDS IN IMMUNOLOGY, 2005, 26 (01) :56-64
[3]   CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2 [J].
Antony, PA ;
Restifo, NP .
JOURNAL OF IMMUNOTHERAPY, 2005, 28 (02) :120-128
[4]   A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma [J].
Attal, M ;
Harousseau, JL ;
Stoppa, AM ;
Sotto, JJ ;
Fuzibet, JG ;
Rossi, JF ;
Casassus, P ;
Maisonneuve, H ;
Facon, T ;
Ifrah, N ;
Payen, C ;
Bataille, R .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (02) :91-97
[5]  
AWWAD M, 1988, IMMUNOLOGY, V65, P87
[6]   CD4+CD25high regulatory cells in human peripheral blood [J].
Baecher-Allan, C ;
Brown, JA ;
Freeman, GJ ;
Hafler, DA .
JOURNAL OF IMMUNOLOGY, 2001, 167 (03) :1245-1253
[7]   Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA-4 expression [J].
Birebent, B ;
Lorho, R ;
Lechartier, H ;
de Guibert, S ;
Alizadeh, M ;
Vu, N ;
Beauplet, A ;
Robillard, N ;
Semana, G .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (12) :3485-3496
[8]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[9]   Comparable engraftment kinetics following peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma [J].
Desikan, KR ;
Barlogie, B ;
Jagannath, S ;
Vesole, DH ;
Siegel, D ;
Fassas, A ;
Munshi, N ;
Singhal, S ;
Mehta, J ;
Tindle, S ;
Nelson, J ;
Bracy, D ;
Mattox, S ;
Tricot, G .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (04) :1547-1553
[10]   Rapid mobilization of CD34+cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma [J].
Devine, SM ;
Flomenberg, N ;
Vesole, DH ;
Liesveld, J ;
Weisdorf, D ;
Badel, K ;
Calandra, G ;
DiPersio, JF .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (06) :1095-1102