scholarly journals Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts

2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiang-Yu Zhao ◽  
Yu-Tong Wang ◽  
Xiao-Dong Mo ◽  
Xiao-Su Zhao ◽  
Ya-Zhe Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Factor G

scholarly journals CD14+ cells in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells induce secretion of interleukin-6 and G-CSF by marrow stroma

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 574-580 ◽  
Author(s):  
M Mielcarek ◽  
BA Roecklein ◽  
B Torok-Storb
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Stimulating Factor ◽  
Mobilized Peripheral Blood ◽  
Factor G

The ability of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs) to induce secretion of cytokines in primary long-term marrow cultures (LTC) or in the human marrow stromal cell line HS23 was compared with that of marrow mononuclear cells. Equal numbers of G-PBMCs or marrow mononuclear cells were added to stromal cultures, supernatants were harvested at day 4 and levels of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, G-CSF, and tumor necrosis factor alpha (TNF alpha) were determined. G- PBMCs induced 21.4-fold higher levels of IL-6 and 12.5-fold higher levels of G-CSF in LTC cocultures compared with marrow mononuclear cells and induced 20.6-fold more IL-6 and 6.3-fold more G-CSF when added to HS23 cells. Experiments using sorted populations of CD20+, CD3+, and CD14+ cells showed that CD14+ cells within G-PBMCs were responsible for triggering the production of IL-6 and G-CSF. The effect did not require cell-cell contact and was inhibited when neutralizing antibodies to IL-1 alpha and IL-1 beta were used in combination. In these experiments, the greater stimulating ability of G-PBMCs is most likely attributable to the greater number of CD14+ cells in G-PBMCs (26.1+% +/- 2.3%) compared with marrow (2.5% +/- 0.8%), because equal numbers of CD14+ cells sorted from marrow and G-PBMCs showed comparable ability to induce IL-6 and G-CSF when placed directly on stromal cells.

scholarly journals Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease

Blood ◽  
1995 ◽  
Vol 86 (12) ◽  
pp. 4422-4429 ◽  
Author(s):  
L Pan ◽  
J Jr Delmonte ◽  
CK Jalonen ◽  
JL Ferrara
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Acute Gvhd ◽  
Cytokine Production ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Graft Versus Host ◽  
Stimulating Factor

The incidence and severity of acute graft-versus-host disease (GVHD) after allogeneic transplantation using peripheral blood progenitor cells mobilized by granulocyte colony-stimulating factor (G-CSF) appear to be no worse than those after bone marrow transplantation, despite the presence of large numbers of T cells in the donor infusion. Experimental studies have shown that type-1 T cells (secreting interleukin-2 [IL-2] and interferon-gamma) mediate acute GVHD, whereas type-2 T cells (secreting IL-4 and IL-10) can prevent acute GVHD. We tested the hypothesis that G-CSF modulates T-cell function toward a type-2 response and thus reduces the severity of acute GVHD. B6 mice were injected with G-CSF or diluent for 4 days, and their splenic T cells were stimulated in vitro with alloantigen or mitogen in the absence of G-CSF. T cells from G-CSF-treated mice showed a significant increase in IL-4 production, with a simultaneous decrease in IL-2 and interferon-gamma production in response to both stimuli. We also examined the effect of G-CSF pretreatment of donors in a GVHD model (B6- ->B6D2F1). Survival was significantly improved in recipients of G-CSF- treated donors. Concanavalin-A-induced cytokine production at day 13 after transplantation also showed an increase in IL-4 along with a decrease in IL-2 and IFN-gamma production by splenocytes from recipients of G-CSF-treated bone marrow and T cells. These data show that pretreatment of donors with G-CSF polarizes donor T cells toward the production of type-2 cytokines, which is associated with reduced type-1 cytokine production and reduced severity of acute GVHD.

Granulocyte Colony-Stimulating Factor Mobilization Affects The Expression Of Regulatory γδ T Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 902-902
Author(s):  
Li Xuan ◽  
Xiuli Wu ◽  
Sijian Yu ◽  
Zhengshan Yi ◽  
Yu Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Science ◽  
Peripheral Blood ◽  
Research Funding ◽  
Γδ T Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Before And After ◽  
Low Incidence ◽  
Stimulating Factor

Abstract Background The immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation. Our previous studies demonstrated that G-CSF mobilization influenced the distribution and clonality of TRGV and TRDV repertoire (T cell receptors of γδ T cells), and significant positive correlation was observed between the invariable clonality of TRDV1 gene repertoire after G-CSF mobilization and low incidence of GVHD in recipients (P=0.015, OR=0.047) (Li Xuan et al. Journal of Translational Medicine 2011). Regulatory γδ T cells (γδ Tregs), which express Foxp3 and primarily belong to CD27+CD25high phenotype, are a novel subset of cells with immunosuppressive function (Xiaoyan Li et al. Journal of Immunology 2012). However, whether G-CSF could influence the expression of γδ Tregs remains unknown. The aim of this study was to investigate the effect of G-CSF mobilization on the expression of γδ Tregs. Methods The immunophenotyping of γδ Tregs was analyzed in peripheral blood mononuclear cells (PBMCs) from 20 donors before and after G-CSF mobilization, using flow cytometry. Results Compared with that before mobilization, the proportions of Vδ1 and CD25+ subsets were significantly increased (P=0.012, P=0.032), whereas the Vδ2 proportion was significantly decreased after G-CSF mobilization (P=0.002). The proportions of total γδ T cells, CD27+ and Foxp3+ subsets were similar between the two groups (P=0.133, P=0.110, P=0.780, respectively). In addition, there was a significant increase in the proportions of Foxp3+Vδ1 and CD25+Foxp3+ subsets (P=0.038, P=0.013), and a significant decrease in the proportions of CD27+Vδ2 and CD25+Vδ2 subsets after G-CSF mobilization (P=0.013, P=0.022). The proportions of CD27+γδ T, CD25+γδ T, Foxp3+γδ T, CD25+CD27+, CD27+Foxp3+, CD27+Vδ1, CD25+Vδ1 and Foxp3+Vδ2 subsets were similar before and after G-CSF mobilization (P=0.422, P=0.342, P=0.724, P=0.070, P=0.503, P=0.053, P=0.386 and P=0.097, respectively). We then compared the Foxp3, CD27 and CD25 phenotypes in total γδ T cells, Vδ1 and Vδ2 subsets. We observed a significant increase in the proportion of CD27+Foxp3+ Vδ1 subsets after G-CSF mobilization (P=0.036). The proportion of CD27+Foxp3+γδ T and CD27+Foxp3+Vδ2 subsets before mobilization were similar to that after mobilization (P=0.539, P=0.507). The proportion of CD25+Foxp3+γδ T, CD25+Foxp3+ Vδ1, CD25+Foxp3+Vδ2, CD25+CD27+γδT, CD25+CD27+Vδ1 and CD25+CD27+ Vδ2 subsets were also similar between the two groups (P=0.249, P=0.539, P=0.507, P=0.934, P=0.209 and P=0.061, respectively). Conclusions G-CSF mobilization significantly increased the proportions of Vδ1 subsets, including Foxp3+Vδ1 and CD27+Foxp3+ Vδ1 subsets, whereas decreased the Vδ2 proportion. Disclosures: Li: This work was supported by Grants from National Natural Science Foundation of China (30871091 and 91129720), the Collaborated grant for HK-Macao-TW of Ministry of Science and Technology (2012DFH30060), the Guangdong Science & Technology Project (2012B0506: Research Funding. Liu: It was supported by 863 Program (No. 2011AA020105).: Research Funding; It was supported by National Public Health Grand Research Foundation (Grant No. 201202017), National Natural Science Foundation of China (Grant No.81000231, No.81270647).: Research Funding; It was supported by Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2484-2490 ◽  
Author(s):  
Mario Arpinati ◽  
Cherie L. Green ◽  
Shelly Heimfeld ◽  
Jill E. Heuser ◽  
Claudio Anasetti
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Dendritic Cells ◽  
Peripheral Blood ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Th2 Responses ◽  
Stimulating Factor

Peripheral blood stem cells (PBSC) obtained from granulocyte-colony stimulating factor (G-CSF)-mobilized donors are increasingly used for allogeneic transplantation. Despite a 10-fold higher dose of transplanted T cells, acute graft-versus-host disease (GVHD) does not develop in higher proportion in recipients of PBSC than in recipients of marrow. T cells from G-CSF-treated experimental animals preferentially produce IL-4 and IL-10, cytokines characteristic of Th2 responses, which are associated with diminished GVHD-inducing ability. We hypothesized that G-CSF-mobilized PBSC contain antigen-presenting cells, which prime T-lymphocytes to produce Th2 cytokines. Two distinct lineages of dendritic cells (DC) have been described in humans, DC1 and DC2, according to their ability to induce naive T-cell differentiation to Th1 and Th2 effector cells, respectively. We have used multicolor microfluorometry to enumerate DC1 and DC2 in the peripheral blood of normal donors. G-CSF treatment with 10 to 16 μg/kg per day for 5 days increased peripheral blood DC2 counts from a median of 4.9 × 106/L to 24.8 × 106/L (P = .0009), whereas DC1 counts did not change. Purified DC1, from either untreated or G-CSF treated donors, induced the proliferation of allogeneic naive T cells, but fresh DC2 were poor stimulators. Tumor necrosis factor- (TNF-)-activated DC1 induced allogeneic naive T cells to produce IFN-γ, which is typical of Th1 responses, whereas TNF--activated DC2 induced allogeneic naive T cells to produce IL-4 and IL-10, which are typical of Th2 responses. PBSC transplants contained higher doses of DC2 than marrow transplants (median, 2.4 × 106/kg versus 0.5 × 106/kg) (P = .006), whereas the dose of DC1 was comparable. Thus, it is conceivable that transplantation of G-CSF-stimulated PBSC does not result in overwhelming acute GVHD because the graft contains predominantly Th2-inducing DC. Adoptive transfer of purified DC2 may be exploited to induce immune deviation after transplantation of hematopoietic stem cells or organ allografts.

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