Combination of C-X-C motif chemokine 9 and C-X-C motif chemokine 10 antibodies with FTY720 prolongs the survival of cardiac retransplantation allografts in a mouse model

Ma, Teng; Xu, Jiacheng; Zhuang, Jiawei; Zhou, Xiaobiao; Lin, Liang; Zhang, Shan; Qi, Zhongquan

doi:10.3892/etm.2015.2204

Cited by 6 publications

(8 citation statements)

References 24 publications

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“…Although previous research by our group demonstrated increased levels of chemokine (C-C motif) ligand 5 and CXCL9 expression as well as secretion in skin-allograft and Tm cell transfer models compared to those in the control groups, those two models are not able to closely mimic the scenario encountered in the clinic due to the absence of blood supply in the skin-allograft model and unsteady factors in the Tm-cell transfer model (14). Therefore, the present study established a new model of two consecutive heterotopic heart transplantations in rats, for which advanced microsurgical technology was used.…”

Section: Introductionmentioning

confidence: 81%

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Deng

et al. 2017

Exp Ther Med

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Abstract. The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8 + Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage. A novel rat model of cardiac re-transplantation was established at 40 days following primary heart transplant. The experiment included two parts, and when models were established, the rats were divided into two groups: Primary cardiac transplant (HTx) and re-transplantation without treatment (HRTx). In part 1, recipients from part 2, including re-transplantation without treatment (HRTx+NS) and re-transplantation treated with anti-CXCL10 antibodies (500 µg every other day by intraperitoneal injection; HRTx+CXCL10 Abs group). The graft survival time was observed and graft infiltration by inflammatory cells was assessed via histology of cardiac graft sections; in addition, the gene expression and the serum concentration of CXCL10 in each group was assessed. Indexes such as rejection-associated cytokines were assayed by reverse-transcription quantitative PCR and ELISA kits, and flow cytometry of splenocytes was used to detect Tm cells in the re-transplantation groups. The results demonstrated that level of CXCL10 was significantly increased and the graft mean survival time was shortened accompanied with aggravated lymphocyte cell infiltration in the HRTx group when compared that in the HTx group; in addition, the serum levels and mRNA expression of interleukin (IL)-2 and interferon (IFN)-γ were increased, while transforming growth factor (TGF)-β was decreased in the HRTx group. Furthermore, neutralization of CXCL10 prolonged the graft mean survival time and delayed accelerated rejection. Compared with that in the HRTx+NS group, serum levels and graft tissue mRNA expression of IFN-γ and IL-2 were decreased in the HRTx+CXCL10 Abs group, while TGF-β mRNA was significantly increased but the serum concentration was not significantly affected. In addition, there was no difference in IL-10 between the two groups, while delayed accelerated rejection paralleled with inflammatory cell infiltration decreased and the proliferation and differentiation of CD8 + Tm cells in secondary lymphoid organs were reduced in the HRTx+CXCL10 Abs group vs. those in the HRTx+NS group. The present study demonstrated that CXCL10 had a crucial role in cardiac transplantation and re-transplantation, and that treatment with CXCL10 antibodies delays accelerated acute rejection mediated by Tm cells in a rat model of cardiac re-transplantation. IntroductionA multidisciplinary program has been initiated to better establish transplantation for prolonging survival time of cardi...

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Section: Introductionmentioning

confidence: 81%

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Deng

et al. 2017

Exp Ther Med

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“…MLR was performed with each MSC line derived from pigs ( n = 3) (less than 1 month old) in triplicate [ 25 – 27 ]. In advance, MSCs used for MLR were identified using both CD mark analysis and in vitro differentiation capacity (adipogenesis and osteogenesis), as described above.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Immunomodulation Properties of Porcine Mesenchymal Stromal/Stem Cells Derived from the Bone Marrow, Adipose Tissue, and Dermal Skin Tissue

Ock

Subbarao

Lee

et al. 2015

Stem Cells International

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Mesenchymal stromal/stem cells (MSCs) demonstrate immunomodulation capacity that has been implicated in the reduction of graft-versus-host disease. Accordingly, we herein investigated the capacity of MSCs derived from several tissue sources to modulate both proinflammatory (interferon [IFN] γ and tumor necrosis factor [TNF] α) and immunosuppressive cytokines (transforming growth factor [TGF] β and interleukin [IL] 10) employing xenogeneic human MSC-mixed lymphocyte reaction (MLR) test. Bone marrow-derived MSCs showed higher self-renewal capacity with relatively slow proliferation rate in contrast to adipose-derived MSCs which displayed higher proliferation rate. Except for the lipoprotein gene, there were no marked changes in osteogenesis- and adipogenesis-related genes following in vitro differentiation; however, the histological marker analysis revealed that adipose MSCs could be differentiated into both adipose and bone tissue. TGFβ and IL10 were detected in adipose MSCs and bone marrow MSCs, respectively. However, skin-derived MSCs expressed both IFNγ and IL10, which may render them sensitive to immunomodulation. The xenogeneic human MLR test revealed that MSCs had a partial immunomodulation capacity, as proliferation of activated and resting peripheral blood mononuclear cells was not affected, but this did not differ among MSC sources. MSCs were not tumorigenic when introduced into immunodeficient mice. We concluded that the characteristics of MSCs are tissue source-dependent and their in vivo application requires more in-depth investigation regarding their precise immunomodulation capacities.

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“…In fact, several studies in renal transplantation have demonstrated a strong association between pre -transplant donor-specific memory T-cells and the development of early AR. (42-44, 61, 62) Further research studying the mechanism responsible for the association between acute rejection and CLAD is clearly needed.…”

Section: Discussionmentioning

confidence: 99%

“…(39-41) Importantly, CXCR3 ligand expression is augmented during the memory immune response and act as a potent chemoattractant for lymphocytes, particularly memory T-cells (CD4, CD8). (42-44)…”

Section: Introductionmentioning

confidence: 99%

Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation

Shino

Weigt

et al. 2017

American Journal of Transplantation

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The impact of allograft injury time-of-onset on the risk of chronic lung allograft dysfunction (CLAD) remains unknown. We hypothesized that episodes of late-onset (≥6 months) allograft injury would produce an augmented CXCR3/ligand immune response, leading to increased CLAD. In a retrospective single-center study, 1894 transbronchial biopsies from 441 lung transplant recipients were reviewed for the presence of acute rejection (AR), lymphocytic bronchiolitis (LB), diffuse alveolar damage (DAD) and organizing pneumonia (OP). The association between the time-of-onset of each injury pattern and CLAD was assessed using multivariable Cox models with time-dependent covariates. BAL CXCR3 ligand concentrations were compared between early and late-onset injury patterns using linear mixed-effects models. Late-onset DAD and OP were strongly associated with CLAD: adjusted HRs 2.8 95%CI 1.5-5.3 and 2.0 95%CI 1.1-3.4, respectively. The early-onset form of these injury patterns did not increase CLAD risk. Late-onset LB and AR predicted CLAD in univariable models, but lost significance after multivariable adjustment for late DAD and OP. AR was the only early-onset injury pattern associated with CLAD development. Elevated BAL CXCR3 ligand concentrations during late-onset allograft injury parallel the increase in CLAD risk and support our hypothesis that late allograft injuries result in a more profound CXCR3/ligand immune response.

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Combination of C-X-C motif chemokine 9 and C-X-C motif chemokine 10 antibodies with FTY720 prolongs the survival of cardiac retransplantation allografts in a mouse model

Cited by 6 publications

References 24 publications

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

Comparison of Immunomodulation Properties of Porcine Mesenchymal Stromal/Stem Cells Derived from the Bone Marrow, Adipose Tissue, and Dermal Skin Tissue

Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation

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