scholarly journals Recombinant Human Granulocyte Colony-Stimulating Factor Significantly Decreases the Expression of CXCR3 and CCR6 on T Cells and Preferentially Induces T helper Cells to a T helper 17 Phenotype in Peripheral Blood Harvests

2009 ◽  
Vol 15 (7) ◽  
pp. 835-843 ◽  
Author(s):  
Li-Xia Sun ◽  
Han-Yun Ren ◽  
Yong-Jin Shi ◽  
Li-Hong Wang ◽  
Zhi-Xiang Qiu
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
T Helper ◽  
T Helper 17 ◽  
Helper Cells ◽  
Stimulating Factor

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.

Patologic IL 17 Producing Helper T Cells In Acute Myeloid Leukemia Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2289-2289
Author(s):  
Gerardo Musuraca ◽  
Serena De Matteis ◽  
Roberta Napolitano ◽  
Francesco Fabbri ◽  
Delia Cangini ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Th17 Cells ◽  
Myeloid Leukemia ◽  
Helper T Cells ◽  
T Helper ◽  
Helper Cells ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) remains the most common form of acute leukemia in adults but the treatments, in the past several decades, have not led to satisfactory results. Serious infections and therapy resistance or relapsed are the main causes of mortality among these patients. IL-17 producing helper T cells (Th17) play in humans, pleiotropic roles in protection against a range of predominantly extracellular bacterial and fungal pathogens, in the pathogenesis of many inflammatory and autoimmune diseases and a controversial role in protection or progression of tumors. In particular, recently has been demonstrated a remarkable plasticity of these cells to transdifferentiate, depending of the stimuli, in a Th1-like Th17 cells (secreting IFNg with tumor suppressor activity) or in a Treg-like Th17 cells (secreting IL-10 with tumor promoter activity). Moreover, few reports indicate that the number of Th17 in patients with hematological malignancies was increased in peripheral blood, however their role and their relationship with respect to other T helper cells, particularly in AML, have not yet been clarified. Our study aims to investigate the role of T helper cells in AML, with particular focus to Th17 cells, hypothesizing their contribution in severe infections developed by these patients and in the high rate of recurrence of the disease. Samples of peripheral blood were collected from 20 newly diagnosed AML patients of any FAB (except promyelocitic) before any treatment and 20 sex and age-matched healthy volunteers. Mononuclear cells (PBMCs) were separated by density gradient centrifugation. Intracellular IFN-γ, IL-17A and IL-4 expression was performed using the human Th1/Th2/Th17 phenotyping kit after stimulation of CD4+ cells with IL-6 (25 μg/ml), phorbol 12-myristate-13-acetate (50 ng/ml) and ionomycin (1 μg/ml). For Tregs analysis, PBMCs were stained with anti-human FITC CD4, APC-Cy7 CD25 and APC Foxp3 and analyzed using a FACSCanto flow cytometer. For the analysis of cytokine secretion, human IL-17 and IL-10 secretion - detection kits were used. Th1 and Th2 percentages were lower in untreated patients (3.4 ± 1.9% and 0.8 ± 0.6% respectively) than in controls (11.6 ± 4.0% and 2.5 ± 1.9% respectively) whereas the Th17 cells were increased in AML patients (1.9 ± 1.2%) in comparison to healthy donors (1.0 ± 0.6) (Fig. 1). All the observed differences were statistically significant. The frequency of CD4+ CD25+ FoxP3+ cells was statistically significant higher in AML samples (5.6 ± 3.0%) than in controls (2.7 ± 0.9%) (Fig 2). Moreover we observed in AML patients, no differences in the frequency of IFN-g/IL-17A double-producing T cells (0.7 ± 0.7%) compared to controls (0.54 ± 0.37%) whereas interestingly we observed an increase in the frequency of IL-10/IL-17A secreting T cells (0.18 ± 0.14% for patients vs. 0.02 ± 0.04% for donors) (Fig. 3). These results strongly suggest the hypothesis that in AML patients, probably through particular stimuli, cancer cells are able to transform the immunological environment (in particular the Th17 activity), towards a state of immunosuppression that promotes the development of infection and reduces the immunological control of the disease and relapses. This finding, if confirmed, could suggest new therapeutic strategies more oriented towards immunomodulation rather than cytoreduction. Disclosures: Martinelli: NOVARTIS, BMS(Consultancy and speaker bureau), PFIZER, ARIAD (Consultancy): Consultancy, Speakers Bureau.

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

Abstract 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.

scholarly journals Chemokine receptor expression on peripheral blood T-helper cells in Helicobacter pylori-associated diseases: chronic gastroduodenitis and peptic ulcer disease

2019 ◽  
Vol 9 (2) ◽  
pp. 295-303
Author(s):  
V. Yu. Talayev ◽  
M. V. Talaeyva ◽  
E. V. Voronina ◽  
I. Ye. Zaichenko ◽  
N. V. Neumoina ◽  
...  
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
T Cell ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Chemokine Receptors ◽  
T Helper ◽  
Helper Cells ◽  
H Pylori

Helicobacter pylorirepresents a pathogen causing chronic infection in around a half of the global human population, which manifestations vary from asymptomatic infection to developing gastritis and peptic ulcer. The data accumulated suggest that overt clinical types of this infection are associated with lost immunoregulation and increased pro-inflammatory cell-mediated immune response triggered byH. pylori-specific T helper cells. Here, we examined the degree of peripheral blood CD4+T cell maturity and related expression of chemokine receptors involved in migration to gastrointestinal tract (CCR9 and CCR6), as well as Тand B-cell zones of lymphoid organs (CCR7 and CXCR5). It was shown that overtH. pylori-infection was coupled to changes in expression pattern of chemokine receptors on T helper cells. In particular, percentage of mature CD4+CD45RO+T cells bearing CCR9 and immature CD4+CD45RO–Т cells expressing CXCR5 was increased in peripheral blood of patients with chronic gastroduodenitis. However, increased amount of activated mature CD4+CD45RO+ICOS+T cells was observed in patients with chronic gastroduodenitis comorbid with peptic ulcer that was also associated with elevated amount of mature CCR6+T helpers (mainly CD4+CD45RO+CCR7–CCR6+cells) and follicular T helper cells as well as emerging minor CD4+CD45RO+CXCR5+CCR6+.T cell subset, not affecting CD4+CCR9+Т cells. Thus, the data obtained evidence that tissue-specific T-helper cell migration is controlled separately in ofH. pylori-associated diseases. 

scholarly journals Granulocyte Colony-Stimulating Factor Reduces the Capacity of Blood Mononuclear Cells to Induce Graft-Versus-Host Disease: Impact on Blood Progenitor Cell Transplantation

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 453-463 ◽  
Author(s):  
Defu Zeng ◽  
Sussan Dejbakhsh-Jones ◽  
Samuel Strober
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Low Density ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Graft Versus Host ◽  
Blood Mononuclear Cells ◽  
Stimulating Factor

The feasibility of transplanting peripheral blood mononuclear cells (PBMC) from granulocyte colony-stimulating factor (G-CSF)–treated normal human donors to myeloablated allogeneic hosts has been demonstrated recently. The current work examined the ability of recombinant G-CSF to alter peripheral blood T-cell function and graft-versus-host disease (GVHD) in a murine model of allogeneic G-CSF–mobilized PBMC transplantation. Administration of recombinant G-CSF to C57BL/Ka mice markedly increased the capacity of PBMC to reconstitute lethally irradiated syngeneic hosts. T- and B-lineage lymphocytes were depleted about 10-fold in the bone marrow of the treated mice, and the T-cell yield in the blood was increased about fourfold. The ability of PBMC or purified CD4+ and CD8+ T cells to induce acute lethal GVHD in irradiated BALB/c mice was reduced after the administration of G-CSF. This was associated with decreased secretion of interferonγ and interleukin-2 (IL-2) and an increased secretion of IL-4. The donor cell inoculum, which was most successful in the rescue of irradiated allogeneic hosts, was the low-density fraction of PBMC from G-CSF–treated mice. These low-density cells were enriched for CD4−CD8−NK1.1+ T cells and secreted about 10-fold more IL-4 than the unfractionated cells from the G-CSF–treated donors.

scholarly journals Granulocyte Colony-Stimulating Factor Reduces the Capacity of Blood Mononuclear Cells to Induce Graft-Versus-Host Disease: Impact on Blood Progenitor Cell Transplantation

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 453-463 ◽  
Author(s):  
Defu Zeng ◽  
Sussan Dejbakhsh-Jones ◽  
Samuel Strober
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Low Density ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Graft Versus Host ◽  
Blood Mononuclear Cells ◽  
Stimulating Factor

Abstract The feasibility of transplanting peripheral blood mononuclear cells (PBMC) from granulocyte colony-stimulating factor (G-CSF)–treated normal human donors to myeloablated allogeneic hosts has been demonstrated recently. The current work examined the ability of recombinant G-CSF to alter peripheral blood T-cell function and graft-versus-host disease (GVHD) in a murine model of allogeneic G-CSF–mobilized PBMC transplantation. Administration of recombinant G-CSF to C57BL/Ka mice markedly increased the capacity of PBMC to reconstitute lethally irradiated syngeneic hosts. T- and B-lineage lymphocytes were depleted about 10-fold in the bone marrow of the treated mice, and the T-cell yield in the blood was increased about fourfold. The ability of PBMC or purified CD4+ and CD8+ T cells to induce acute lethal GVHD in irradiated BALB/c mice was reduced after the administration of G-CSF. This was associated with decreased secretion of interferonγ and interleukin-2 (IL-2) and an increased secretion of IL-4. The donor cell inoculum, which was most successful in the rescue of irradiated allogeneic hosts, was the low-density fraction of PBMC from G-CSF–treated mice. These low-density cells were enriched for CD4−CD8−NK1.1+ T cells and secreted about 10-fold more IL-4 than the unfractionated cells from the G-CSF–treated donors.

scholarly journals Suppression of Alloantigen-Induced T-Cell Proliferation by CD14+ Cells Derived From Granulocyte Colony-Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1629-1634 ◽  
Author(s):  
Marco Mielcarek ◽  
Paul J. Martin ◽  
Beverly Torok-Storb
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cd4 Cells ◽  
Peripheral Blood Mononuclear ◽  
Donor T Cells ◽  
Low Incidence ◽  
Stimulating Factor

Abstract The proliferative responsiveness of granulocyte colony-stimulating factor (G-CSF )–mobilized blood was studied in uni-directional mixed leukocyte cultures. Unfractionated mononuclear cells from mobilized blood obtained by leukapheresis at day 4 after initiation of G-CSF (G-PBMC) were hyporesponsive (31.5% ± 9.2% response, P = .003) compared to mononuclear cells obtained from the peripheral blood before administration of G-CSF (preG-PBMC). There was great variability among donors when purified preG- and G-CD4 cells were compared. In eight of 10 donors, G-CD4 cells were equally responsive or moderately hyporesponsive; in two of 10 donors, G-CD4 cells were more strikingly hyporesponsive. CD14 cells derived from leukapheresis products (G-CD14 cells) suppressed alloantigen-induced proliferation by 48.6% ± 7.5% when added to preG-PBMC or preG-CD4 cells at responder-CD14 ratios of 2:1 (P < .001). Suppression was evident (14.4% ± 5.0%) even at responder-CD14 ratios of 8:1 and was largely contact-independent. PreG- and G-CD14 cells had equivalent potency in suppressing proliferative responses. Given that G-CSF–mobilized blood cell grafts contain 50-fold more CD14 cells and only 10-fold more T cells than marrow, we propose that suppression of donor T cells by the large proportion of monocytes present in leukapheresis products could contribute to the unexpectedly low incidence and severity of graft-versus-host disease after peripheral blood stem cell transplantation.

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