Characterization of peripheral blood stem cell grafts mobilized by granulocyte colony-stimulating factor and plerixafor compared with granulocyte colony-stimulating factor alone

• Published in: Cytotherapy (Oxford, England) Vol. 15; no. 7; pp. 861 - 868
• Main Authors: Gaugler, Beatrice, Arbez, Jessy, Legouill, Steven, Tiberghien, Pierre, Moreau, Philippe, Derenne, Sophie, Saas, Philippe, Mohty, Mohamad
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-07-2013
• Subjects: Adolescent; Adult; Advanced Basic Science; Antigens, Surface - metabolism; Blood Component Removal - methods; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Child; Child, Preschool; dendritic cells; Dendritic Cells - cytology; Dendritic Cells - metabolism; Female; Forkhead Transcription Factors - metabolism; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - metabolism; Heterocyclic Compounds - administration & dosage; Heterocyclic Compounds - metabolism; HLA-DR Antigens - immunology; Humans; immune effectors; Interferon-gamma - metabolism; Male; Middle Aged; mobilization; Other; Peripheral Blood Stem Cell Transplantation; peripheral blood stem cells; plerixafor; Transplants - drug effects; Transplants - metabolism; Tumor Necrosis Factor-alpha - metabolism; plerixafor; dendritic cells; mobilization; immune effectors; peripheral blood stem cells
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2013.03.013

Abstract Background aims This study aimed to characterize the immune effectors contained in apheresis samples obtained from patients with grafts mobilized with plerixafor and granulocyte colony-stimulating factor (G-CSF) (P+G) compared with grafts mobilized with G-CSF alone (G). Methods Aliquots of apheresis samples were obtained from 36 patients with malignant diseases after mobilization with G (n = 18) or P+G (n = 18). The phenotype and cytokine secretion profile of T cell and dendritic cell subsets were characterized by multicolor cytometry including intracellular cytokine staining. Results In grafts collected after mobilization with P+G, there was a significantly higher percentage of CD3+ T cells compared with samples collected after mobilization with G alone. On a functional level, a significant increase of interferon-γ and tumor necrosis factor-α secreting CD8+ T cells was observed in the P+G group compared with the G group. CD4+ Foxp3+ regulatory T cells were similar in both groups but exhibited a lower expression of inducible costimulatory molecule and a significantly higher expression of CD127 in the P+G group. Myeloid dendritic cells (MDCs) and BDCA3+ dendritic cells were similar in both groups. In contrast, plasmacytoid dendritic cells (PDCs) (CD123+ BDCA2+ HLA-DR+ ) were significantly increased in the P+G grafts, leading to a higher PDC-to-MDC ratio. PDCs mobilized by P+G displayed different functional markers—a higher percentage of ILT7+ PDCs and decreased expression of CD86—suggesting a potential regulatory capacity of PDCs mobilized by P+G. Conclusions Grafts mobilized with P+G exhibited major different functional features compared with grafts mobilized with G alone, suggesting that such grafts may have an impact on patient outcome after autologous stem cell transplantation.