Differential effects of G-CSF mobilisation on dendritic cell subsets in normal allogeneic donors and patients undergoing autologous transplantation

Abstract

Summary:It has been suggested that the immunological properties of cytokine primed PBSC may reflect the presence of altered levels of cellular components. In this study the changes induced in blood dendritic cell (DC) subsets following G-CSF mobilisation are analysed. Analysis of normal donors (n = 64) demonstrated considerable individual variation in the absolute numbers (؋10 6 /l) of resting blood CD11c ؊ DC (1.2-26.2) and CD11c + DC (0.9-34.7) as well as in the CD11c ؊ /CD11c + DC ratio (0.29-4.13). G-CSF therapy increased CD11c ؊ DC numbers to above the normal range in all normal donors analysed (n = 6) and the CD11c ؊ /CD11c + ratio was also increased to Ͼ2.0 in all donors. Patients undergoing autologous PBSCT showed a heterogeneous response to mobilisation and although total DC and CD11c ؊ DC numbers were increased in the majority (8/14), they remained within the normal range post mobilisation. The CD11c ؊ /CD11c + ratio decreased in 5/15 patients and only three patients had ratios Ͼ2.0 post mobilisation. Post G-CSF the DC from all normal donors and 13/14 patients had an immature phenotype. These results demonstrate that G-CSF mobilisation induces relatively consistent changes in the number and ratio of DC subsets in normal donors, but considerable variation is seen in the response of patients undergoing mobilisation for autologous PBSCT.

Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected

“…For example, GM-CSF will (a) enhance the tumor-directed lytic ability of PBMNC; (b) activate macrophages and (c) mediate the proliferation, maturation and migration of dendritic cells. In addition, GM-CSF mobilization may enhance innate and acquired immunity after transplant, because it decreases the number of type 2 dendritic cells (DC2) within the mobilized cells (30,31). These dendritic cells may inhibit cellular immune responses.…”

Improved Mobilization of Peripheral Blood CD34+Cells and Dendritic Cells by AMD3100 plus Granulocyte–Colony-Stimulating Factor in Non-Hodgkin's Lymphoma Patients

“…We and others have studied the polarization of DC subsets during PBSC mobilization with G-CSF in normal donors (22)(23)(24)(25) for allogeneic transplantation and in cancer patients (26). Several groups reported polarization to pDC2 cells in normal donors receiving G-CSF for mobilization (22)(23)(24)28,29), whereas others did not find polarization to pDC2 (26,27,30).…”

“…It has been reported that mobilization of PBSCs with G-CSF results with polarization of DCs to pDC2-type DC subset, resulting with an increase in Th2-type over Th1-type T cell response with a potential for a decrease in overall T cell cytotoxicity (23)(24)(25)(26)(27)(28)(29)(30). Because the effect of AMD3100 on mobilization of DCs was never tested before, we decided to test the effect of adding AMD3100 to NHL patients mobilized with G-CSF on blood pDC1 and pDC2 cells.…”

Effect of hematopoietic growth factors on severity of experimental autoimmune encephalomyelitis

“…24,[34][35][36] G-CSF, although regarded by some as a Th2-inducing cytokine, seems to have inconsistent effects in terms of Th1/Th2 skewing. It has been shown that G-CSF can exert immunomodulatory effects on T lymphocytes and affect the production of IFN-g and IL-4, possibly owing to the preferential mobilization of Th2-inducing DCs.…”