scholarly journals Immune Cell Subset Counts Associated with Graft-versus-Host Disease

2014 ◽  
Vol 20 (4) ◽  
pp. 450-462 ◽  
Author(s):  
Peter J. Podgorny ◽  
Yiping Liu ◽  
Poonam Dharmani-Khan ◽  
Laura M. Pratt ◽  
Kareem Jamani ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Immune Cell ◽  
Cell Subset ◽  
Immune Cell Subset ◽  
Host Disease ◽  
Graft Versus Host

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

scholarly journals Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease—a gut feeling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Gavin ◽  
Erik Boberg ◽  
Lena Von Bahr ◽  
Matteo Bottai ◽  
Anton Törnqvist Andrén ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Profile ◽  
Acute Graft

AbstractAcute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment.Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy.Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.

scholarly journals Interleukin-2 inhibits graft-versus-host disease-promoting activity of CD4+ cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2560-2569 ◽  
Author(s):  
M Sykes ◽  
MW Harty ◽  
GL Szot ◽  
DA Pearson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Spleen Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Subset ◽  
Graft Versus Leukemia

Abstract We have recently shown that a short course of high-dose interleukin-2 (IL-2) can markedly inhibit the graft-versus-host disease (GVHD)- promoting activity of donor CD4+ T cells. The difficulty in dissociating GVHD-promoting from graft-versus-leukemia (GVL) effects of alloreactive donor T cells currently prevents clinical bone marrow transplantation (BMT) from fulfilling its full potential. To test the capacity of IL-2 treatment to promote such a dissociation, we have developed a new murine transplantable acute myelogenous leukemia model using a class II major histocompatibility complex-positive BALB/c Moloney murine leukemia virus-induced promonocytic leukemia, 2B-4–2. BALB/c mice receiving 2.5 x 10(5) 2B-4–2 cells intravenously 1 week before irradiation and syngeneic BMT died from leukemia within 2 to 4 weeks after BMT. Administration of syngeneic spleen cells and/or a 2.5- day course of IL-2 treatment alone did not inhibit leukemic mortality. In contrast, administration of non-T-cell-depleted fully allogeneic B10 (H-2b) spleen cells and T-cell-depleted B10 marrow led to a significant delay in leukemic mortality in IL-2-treated mice. In these animals GVHD was inhibited by IL-2 treatment. GVL effects were mediated entirely by donor CD4+ and CD8+ T cells. Remarkably, IL-2 administration did not diminish the magnitude of the GVL effect of either T-cell subset. This was surprising, because CD4-mediated GVHD was inhibited in the same animals in which CD4-mediated GVL effects were not reduced by IL-2 treatment. These results suggest a novel mechanism by which GVHD and GVL effects of a single unprimed alloreactive T-cell subset can be dissociated; different CD4 activities promote GVHD and GVL effects, and the former, but not the latter activities are inhibited by treatment with IL-2.

scholarly journals An activated Th17-prone T cell subset involved in chronic graft-versus-host disease sensitive to pharmacological inhibition

JCI Insight ◽  
2017 ◽  
Vol 2 (12) ◽  
Author(s):  
Edouard Forcade ◽  
Katelyn Paz ◽  
Ryan Flynn ◽  
Brad Griesenauer ◽  
Tohti Amet ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Cell Subset ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Subset ◽  
Pharmacological Inhibition

scholarly journals Interleukin-2 inhibits graft-versus-host disease-promoting activity of CD4+ cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2560-2569 ◽  
Author(s):  
M Sykes ◽  
MW Harty ◽  
GL Szot ◽  
DA Pearson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Spleen Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Subset ◽  
Graft Versus Leukemia

We have recently shown that a short course of high-dose interleukin-2 (IL-2) can markedly inhibit the graft-versus-host disease (GVHD)- promoting activity of donor CD4+ T cells. The difficulty in dissociating GVHD-promoting from graft-versus-leukemia (GVL) effects of alloreactive donor T cells currently prevents clinical bone marrow transplantation (BMT) from fulfilling its full potential. To test the capacity of IL-2 treatment to promote such a dissociation, we have developed a new murine transplantable acute myelogenous leukemia model using a class II major histocompatibility complex-positive BALB/c Moloney murine leukemia virus-induced promonocytic leukemia, 2B-4–2. BALB/c mice receiving 2.5 x 10(5) 2B-4–2 cells intravenously 1 week before irradiation and syngeneic BMT died from leukemia within 2 to 4 weeks after BMT. Administration of syngeneic spleen cells and/or a 2.5- day course of IL-2 treatment alone did not inhibit leukemic mortality. In contrast, administration of non-T-cell-depleted fully allogeneic B10 (H-2b) spleen cells and T-cell-depleted B10 marrow led to a significant delay in leukemic mortality in IL-2-treated mice. In these animals GVHD was inhibited by IL-2 treatment. GVL effects were mediated entirely by donor CD4+ and CD8+ T cells. Remarkably, IL-2 administration did not diminish the magnitude of the GVL effect of either T-cell subset. This was surprising, because CD4-mediated GVHD was inhibited in the same animals in which CD4-mediated GVL effects were not reduced by IL-2 treatment. These results suggest a novel mechanism by which GVHD and GVL effects of a single unprimed alloreactive T-cell subset can be dissociated; different CD4 activities promote GVHD and GVL effects, and the former, but not the latter activities are inhibited by treatment with IL-2.

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