scholarly journals Compound a Increases Cell Infiltration in Target Organs of Acute Graft-versus-Host Disease (aGVHD) in a Mouse Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4237
Author(s):  
Abdellatif Bouazzaoui ◽  
Ahmed A. H. Abdellatif ◽  
Faisal A. Al-Allaf ◽  
Neda M. Bogari ◽  
Mohiuddin M. Taher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Graft Versus Host Disease ◽  
Cell Infiltration ◽  
Compound A ◽  
Host Disease ◽  
Graft Versus Host ◽  
Target Organs ◽  
Acute Graft

Systemic steroids are used to treat acute graft-versus-host disease (aGVHD) caused by allogenic bone marrow transplantation (allo-BMT); however, their prolonged use results in complications. Hence, new agents for treating aGVHD are required. Recently, a new compound A (CpdA), with anti-inflammatory activity and reduced side effects compared to steroids, has been identified. Here, we aimed to determine whether CpdA can improve the outcome of aGVHD when administered after transplantation in a mouse model (C57BL/6 in B6D2F1). After conditioning with 9Gy total body irradiation, mice were infused with bone marrow (BM) cells and splenocytes from either syngeneic (B6D2F1) or allogeneic (C57BL/6) donors. The animals were subsequently treated (3 days/week) with 7.5 mg/kg CpdA from day +15 to day +28; the controls received 0.9% NaCl. Thereafter, the incidence and severity of aGVHD in aGVHD target organs were analyzed. Survival and clinical scores did not differ significantly; however, CpdA-treated animals showed high cell infiltration in the target organs. In bulk mixed lymphocyte reactions, CpdA treatment reduced the cell proliferation and expression of inflammatory cytokines and chemokines compared to controls, whereas levels of TNF, IL-23, chemokines, and chemokine receptors increased. CpdA significantly reduced proliferation in vitro but increased T cell infiltration in target organs.

scholarly journals Cyclosporine A and IFNγ licencing enhances human mesenchymal stromal cell potency in a humanised mouse model of acute graft versus host disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jennifer M. Corbett ◽  
Ian Hawthorne ◽  
Hazel Dunbar ◽  
Ivan Coulter ◽  
Mairead Ni Chonghaile ◽  
...  
Keyword(s):  
Mouse Model ◽  
Graft Versus Host Disease ◽  
Cyclosporine A ◽  
Limiting Factor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cytokine Activation ◽  
Acute Graft

AbstractImmunosuppressive ability in human MSC donors has been shown to be variable and may be a limiting factor in MSC therapeutic efficacy in vivo. The importance of cytokine activation of mesenchymal stromal cells (MSCs) to facilitate their immunosuppressive function is well established. This study sought to further understand the interactions between MSCs and the commonly used calcineurin inhibitor cyclosporine A (CsA). The existing literature regarding approaches that use MSCs and cyclosporine are conflicting regarding the effect of CsA on MSC potency and function. Here, we clearly demonstrate that when added at the same time as MSCs, CsA negatively affects MSC suppression of T cell proliferation. However, licencing MSCs with IFNγ before addition of CsA protects MSCs from this negative effect. Notably, adding CsA to MSCs after IFNγ pre-stimulation enhances MSC production of IDO. Mechanistically, we identified that CsA reduces SOCS1 expression to facilitate enhanced IDO production in IFNγ pre-stimulated MSCs. Importantly, CsA exposure to IFNγ pre-stimulated MSC before administration, significantly enhanced the potency of MSCs in a human relevant humanised mouse model of acute Graft versus Host Disease. In summary, this study identified a novel licencing strategy to enhance MSC potency in vitro and in vivo.

scholarly journals Donor-type CD4+CD25+ Regulatory T Cells Suppress Lethal Acute Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation

2002 ◽  
Vol 196 (3) ◽  
pp. 389-399 ◽  
Author(s):  
Petra Hoffmann ◽  
Joerg Ermann ◽  
Matthias Edinger ◽  
C. Garrison Fathman ◽  
Samuel Strober
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Treg Cells ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor Type ◽  
Acute Graft

Acute graft-versus-host disease (aGVHD) is still a major obstacle in clinical allogeneic bone marrow (BM) transplantation. CD4+CD25+ regulatory T (Treg) cells have recently been shown to suppress proliferative responses of CD4+CD25− T cells to alloantigenic stimulation in vitro and are required for ex vivo tolerization of donor T cells, which results in their reduced potential to induce aGVHD. Here we show that CD4+CD25+ T cells isolated from the spleen or BM of donor C57BL/6 (H-2b) mice that have not been tolerized are still potent inhibitors of the alloresponse in vitro and of lethal aGVHD induced by C57BL/6 CD4+CD25− T cells in irradiated BALB/c (H-2d) hosts in vivo. The addition of the CD4+CD25+ Treg cells at a 1:1 ratio with responder/inducer CD4+CD25− T cells resulted in a >90% inhibition of the mixed leukocyte reaction and marked protection from lethal GVHD. This protective effect depended in part on the ability of the transferred CD4+CD25+ T cells to secrete interleukin 10 and occurred if the Treg cells were of donor, but not host, origin. Our results demonstrate that the balance of donor-type CD4+CD25+ Treg and conventional CD4+CD25− T cells can determine the outcome of aGVHD.

scholarly journals Induction of oral tolerance in bone marrow transplantation recipients suppresses graft-versus-host disease in a semiallogeneic mouse model

2003 ◽  
Vol 32 (4) ◽  
pp. 363-369 ◽  
Author(s):  
A Nagler ◽  
M Ohana ◽  
R Alper ◽  
V Doviner ◽  
Y Sherman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Mouse Model ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Oral Tolerance ◽  
Host Disease ◽  
Graft Versus Host

A safety and feasibility study with platelet lysate expanded bone marrow mesenchymal stromal cells for the treatment of acute graft-versus-host disease in Brazil

2013 ◽  
Vol 55 (5) ◽  
pp. 1203-1205 ◽  
Author(s):  
Lucia Silla ◽  
Vanessa Valim ◽  
Bruna Amorin ◽  
Ana Paula Alegretti ◽  
Fernanda dos Santos de Oliveira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Feasibility Study ◽  
Mesenchymal Stromal Cells ◽  
Graft Versus Host Disease ◽  
Stromal Cells ◽  
Platelet Lysate ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals Protective effect of neutralizing anti-IL-18α monoclonal antibody on a mouse model of acute graft-versus-host disease

2015 ◽  
Vol 34 (4) ◽  
pp. 2031-2039 ◽  
Author(s):  
XIAOCUI LI ◽  
CUIPING ZHANG ◽  
WEI CHEN ◽  
BIN PAN ◽  
FANYUN KONG ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mouse Model ◽  
Protective Effect ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft
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