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Functional Regulatory T Cells Are Collected in Stem Cell Autografts by Mobilization with High-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor¹

Maud Condomines^*,,, Philippe Quittet, Zhao-Yang Lu^¶, Laure Nadal^*, Pascal Latry, Ernesto Lopez, Marion Baudard, Guilhem Requirand^*, Christophe Duperray^*,, Jean-François Schved^,¶, Jean-François Rossi^,, Karin Tarte and Bernard Klein^2,*,,,¶

^* Institute of Research in Biotherapy, Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier, France; Université Montpellier1, Montpellier, France; Institut National de la Sante et de la Recherche Medicale (INSERM), Montpellier, France; Department of Hematology and Clinical Oncology, CHU Montpellier, Montpellier, France; and ^¶ Unit for Cellular Therapy, CHU Montpellier, Montpellier, France

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.

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The JI 2006 176: 6365-6366. [Full Text]  

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