scholarly journals Erratum to “Granulocyte Colony-Stimulating Factor-Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease” [Biol Blood Marrow Transplant 22(2016):658-668]

2016 ◽  
Vol 22 (7) ◽  
pp. 1341
Author(s):  
Sumithira Vasu ◽  
Susan Geyer ◽  
Anissa Bingman ◽  
Jeffery J. Auletta ◽  
Samantha Jaglowski ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Immune Cell ◽  
Marrow Transplant ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Immune Cell Subsets ◽  
Stimulating Factor

Granulocyte Colony-Stimulating Factor Induced Acute and Chronic Graft-Versus-Host Disease

2010 ◽  
Vol 90 (9) ◽  
pp. 1022-1029 ◽  
Author(s):  
Olle Ringden ◽  
Zuzana Hassan ◽  
Helen Karlsson ◽  
Richard Olsson ◽  
Brigitta Omazic ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Stimulating Factor

scholarly journals POS0176 COMBINING CXCL5 WITH CONVENTIONAL THERAPY PROVIDES DURABLE IMMUNOSUPPRESSION IN MURINE LUPUS NEPHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 301.1-301
Author(s):  
X. Fan ◽  
D. Guo ◽  
F. Lim ◽  
J. Thumboo ◽  
W. Hwang ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Combination Therapy ◽  
Graft Versus Host Disease ◽  
Conventional Therapy ◽  
Immune Cell ◽  
Marrow Transplant ◽  
High Concentration ◽  
Host Disease ◽  
Graft Versus Host ◽  
Luminex Technology

Background:Lupus nephritis (LN) is a condition arising from abnormal immune responses to internal organs. Patients with LN suffer from severe morbidity and mortality1, 2. Despite the aggressive regimen, 20-40% of patients do not respond to current conventional therapy. CXCL5, as a potent chemoattractant and activator of neutrophils3, demonstrates strong immunosuppression in the pre-clinical mouse model of graft versus host disease (GvHD)4 and lupus nephritis (LN) by intravenous administration.Objectives:In this study, we aim to evaluate whether the therapeutic effect of conventional therapy could be further improved by combination therapy with CXCL5.Methods:Ten doses of exogenous CXCL5 (3ug/kg, biweekly) together with conventional therapy (methylprednisolone (MP, intravenous (IV) injection with 8.3mg/kg/day at day-1, day-2 and day-3) + cyclophosphamide (CP, IV injection with 0.5g/BSA at day-4, monthly for 5 doses)) were administered to 8-week-old Faslpr mice by IV injection. Mice were monitored for 64 weeks. Splenic immune profile at 3 weeks post treatment (PT) was measured by flow cytometry. Circulating cytokine profile were detected by Luminex technology. Renal function was evaluated by urinary spot albumin creatinine ratio. In situ renal immune cell infiltration and complement 3 deposition were detected by Haematoxylin and Eosin (H&E) and immunohistochemistry staining.Results:Comparing to control mice (dPBS: 0% at 28 weeks PT), mice survival was improved to 100% at 40 weeks PT and 55.6% at 64 weeks PT by combination therapy of CXCL5 and conventional therapy (MP + CP) (p<0.0001). The accumulation of autoantibody (anti-dsDNA) and proteinuria were reduced 61.2-fold at 32 weeks PT (p=0.004) and 83.5-fold at 28 weeks PT (p=0.03) respectively. Both autoantibody and proteinuria were maintained at low level for 64 weeks. The classification of LN was significantly reduced at 10 weeks PT and equivalent to the classes we observed in pre-onset mice (p=0.004). Although combination therapy was not able to promote Tregs, it reduced both innate (neutrophils and macrophages) and adaptive (TH1, TH2 and TH17 cells and B cells) immunities significantly. Concomitantly, the serum level of endogenous CXCL5 was boosted up by exogenous administration from 74.2 +/- 53.9 pg/ml to 254.1 +/- 147.1 pg/ml at 8 weeks PT (p=0.05) and this relative high concentration was maintained for 48 weeks.Conclusion:Combining CXCL5 with conventional therapy provides effective and durable immunosuppression in murine LN and it may provide a new option for LN therapy.References:[1]Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. May 8 2017;12(5):825-835. doi:10.2215/cjn.05780616.[2]Touma Z, Gladman DD. Current and future therapies for SLE: obstacles and recommendations for the development of novel treatments. Lupus Sci Med. 2017;4(1):e000239. doi:10.1136/lupus-2017-000239.[3]Koltsova EK, Ley K. The mysterious ways of the chemokine CXCL5. Immunity. Jul 23 2010;33(1):7-9. doi:10.1016/j.immuni.2010.07.012.[4]Fan X, Guo D, Cheung AMS, et al. Mesenchymal Stromal Cell (MSC)-Derived Combination of CXCL5 and Anti-CCL24 Is Synergistic and Superior to MSC and Cyclosporine for the Treatment of Graft-versus-Host Disease. Biol Blood Marrow Transplant. Jun 5 2018;doi:10.1016/j.bbmt.2018.05.029.Disclosure of Interests:None declared

Granulocyte Colony-Stimulating Factor–Mobilized Allogeneic Stem Cell Transplantation Maintains Graft-Versus-Leukemia Effects Through a Perforin-Dependent Pathway While Preventing Graft-Versus-Host Disease

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4071-4078 ◽  
Author(s):  
Luying Pan ◽  
Takanori Teshima ◽  
Geoffrey R. Hill ◽  
David Bungard ◽  
Yani S. Brinson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
Stimulating Factor ◽  
Ctl Activity

Abstract Minimization of graft-versus-host disease (GVHD) with preservation of the graft-versus-leukemia (GVL) effect is a crucial step to improve the overall survival of allogeneic bone marrow transplantation (BMT) for patients with hematological malignancies. We and other investigators have shown that granulocyte colony-stimulating factor (G-CSF)–mobilized allogeneic peripheral stem cell transplantation (PBSCT) reduces the severity of acute GVHD in murine models. In this study, we investigated whether G-CSF–mobilized PBSC maintain their GVL effect in a murine allogeneic transplant model (B6 → B6D2F1). B6 mice (H-2b) were injected subcutaneously with human G-CSF (100 μg/kg/d) for 6 days and their splenocytes were harvested on day 7 as a source of PBSC. G-CSF mobilization dramatically improved transplant survival compared with nonmobilized controls (95% v0%, P &lt; .001). Systemic levels of lipopolysaccharide and tumor necrosis factor- were markedly reduced in recipients of allogeneic G-CSF–mobilized donors, but cytolytic T lymphocyte (CTL) activity against host tumor target cells p815 was retained in those recipients. When leukemia was induced in recipients by coinjection of p815 tumor cells (H-2d) at the time of transplantation, all surviving recipients of G-CSF–mobilized B6 donors were leukemia-free at day 70 after transplant, whereas all mice who received T-cell–depleted (TCD) splenocytes from G-CSF–mobilized B6 donors died of leukemia. When splenocytes from G-CSF–mobilized perforin-deficient (pfp−/−) mice were used for transplantation, 90% of recipients died of leukemia, demonstrating that perforin is a crucial pathway mediating GVL effects after G-CSF–mobilized PBSCT. These data illustrate that G-CSF–mobilized allogeneic PBSCT separate GVL from GVHD by preserving perforin-dependent donor CTL activity while reducing systemic inflammation.

Granulocyte Colony-Stimulating Factor–Mobilized Allogeneic Stem Cell Transplantation Maintains Graft-Versus-Leukemia Effects Through a Perforin-Dependent Pathway While Preventing Graft-Versus-Host Disease

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4071-4078 ◽  
Author(s):  
Luying Pan ◽  
Takanori Teshima ◽  
Geoffrey R. Hill ◽  
David Bungard ◽  
Yani S. Brinson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
Stimulating Factor ◽  
Ctl Activity

Minimization of graft-versus-host disease (GVHD) with preservation of the graft-versus-leukemia (GVL) effect is a crucial step to improve the overall survival of allogeneic bone marrow transplantation (BMT) for patients with hematological malignancies. We and other investigators have shown that granulocyte colony-stimulating factor (G-CSF)–mobilized allogeneic peripheral stem cell transplantation (PBSCT) reduces the severity of acute GVHD in murine models. In this study, we investigated whether G-CSF–mobilized PBSC maintain their GVL effect in a murine allogeneic transplant model (B6 → B6D2F1). B6 mice (H-2b) were injected subcutaneously with human G-CSF (100 μg/kg/d) for 6 days and their splenocytes were harvested on day 7 as a source of PBSC. G-CSF mobilization dramatically improved transplant survival compared with nonmobilized controls (95% v0%, P < .001). Systemic levels of lipopolysaccharide and tumor necrosis factor- were markedly reduced in recipients of allogeneic G-CSF–mobilized donors, but cytolytic T lymphocyte (CTL) activity against host tumor target cells p815 was retained in those recipients. When leukemia was induced in recipients by coinjection of p815 tumor cells (H-2d) at the time of transplantation, all surviving recipients of G-CSF–mobilized B6 donors were leukemia-free at day 70 after transplant, whereas all mice who received T-cell–depleted (TCD) splenocytes from G-CSF–mobilized B6 donors died of leukemia. When splenocytes from G-CSF–mobilized perforin-deficient (pfp−/−) mice were used for transplantation, 90% of recipients died of leukemia, demonstrating that perforin is a crucial pathway mediating GVL effects after G-CSF–mobilized PBSCT. These data illustrate that G-CSF–mobilized allogeneic PBSCT separate GVL from GVHD by preserving perforin-dependent donor CTL activity while reducing systemic inflammation.

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