Granulocyte colony-stimulating factor (G-CSF) transiently suppresses mitogen-stimulated T-cell proliferative response

Abstract

Summary Granulocyte colony-stimulation factor (G-CSF) is a cytokine that selectively promotes growth and maturation of neutrophils and may modulate the cytokine response to inflammatory stimuli. The purpose of this study was to examine the effect of G-CSF on ex vivo peripheral blood mononuclear cell (PBMC) functions. Ten patients with breast cancer were included in a clinical trial in which r-metHuG-CSF was administrered daily for 5 days to mobilize peripheral blood stem cells. Ten healthy women were also included as controls. Our data show that G-CSF treatment induces an increase in peripheral blood leucocyte, neutrophil, lymphocyte and monocyte counts. We have found a modulation in the percentages of CD19+, CD45+CD14+, CD4+CD45RA+ and CD4+CD45RO+ cells in PBMC fractions during G-CSF treatment. We have also found a significant reduction in the proliferative response of PBMC to mitogenic stimulation that reverted 14 days after the fifth and the last dose of G-CSF. Furthermore, it was not associated with significant changes in the pattern of cytokine production. The mechanism of this immunoregulatory effect is probably indirect since G-CSF receptor has not been found in T lymphocytes. This mechanism and its potential clinical applications remain to be elucidated.

G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases

“…[7][8][9][10] After G-CSF stimulation in vivo, human and murine T cells show a reduced cytotoxic activity and proliferative response upon in vitro stimulation. 11,12 Monocytes from G-CSF-mobilized human donors have also been shown to suppress T-cell alloreactivity. 11 This suppresion may occur through an interleukin-10 (IL-10)-dependent mechanism 13 and/or through the inhibition of IL-12 and tumor necrosis factor ␣ (TNF-␣) release.…”

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

“…6,7 In vitro human studies have demonstrated that PBSC products have high levels of T cell inhibitory activity. [8][9][10][11][12][13] This effect has been variously attributed to the high levels of IL-10 produced by monocytes, 14 to modulation of monocyte function, 15 and more recently, to a mobilisation-associated increase in certain dendritic cell (DC) subsets. 16,17 DC constitute a system of antigen-presenting cells that play a critical role in regulating immune responses.…”

G-CSF mobilized vs conventional donor lymphocytes for therapy of relapse or incomplete engraftment after allogeneic hematopoietic transplantation

“…35 After in vivo administration of G-CSF, human and murine peripheral blood T cells have shown reduced cytotoxic activity and proliferative response upon in vitro stimulation. 36 Monocytes of peripheral blood from G-CSF-mobilized human donors have also been shown to suppress T-cell allo-reactivity. This suppression may occur through an IL-10-dependent mechanism, downregulation of CD28/B7(CD80 and CD86) co-stimulatory molecules signals and/or through the inhibition of IL-12 and TNF-alpha release.…”