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Endoplasmic reticulum stress-mediated apoptosis involved in indirect recognition pathway blockade induces long-term heart allograft survival.

Xiang J, Gu X, Qian S, Chen Z - J. Biomed. Biotechnol. (2010)

Bottom Line: This approach could specifically and effectively knock down CD80 and CD86 expression.We also found a higher percentage of apoptotic T cells in lymph tissues and grafts than that detected in control group.Our results indicated that ERS-induced apoptosis may be involved in allogeneic T-cell apoptosis, and the ERS-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of allograft rejection.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.

ABSTRACT
Implementation of dendritic cell- (DC-) based therapies in organ transplantation can reduce dependency on nonspecific immunosuppression. Despite extensive research, mechanisms of equipped DCs inducing transplant tolerance remain incomplete. Here, we applied RNA interference technique to inhibit CD80 and CD86 expression in host bone marrow-derived DCs. This approach could specifically and effectively knock down CD80 and CD86 expression. T cells primed by these DCs inhibited allogeneic responses. Administration of recipient DCs loaded with alloantigen after CD80 and CD86 blockade prolonged cardiac allograft survival. We also found a higher percentage of apoptotic T cells in lymph tissues and grafts than that detected in control group. In addition, these T cells expressed high expression of GRP78 than controls, indicating activation of unfolded protein responses. Upregulation of CHOP expression among these cells suggested that the endoplasmic reticulum stress (ERS) response switched to a proapoptotic response. Our results indicated that ERS-induced apoptosis may be involved in allogeneic T-cell apoptosis, and the ERS-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of allograft rejection.

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Related in: MedlinePlus

T cells isolated on day 5 after translation from the spleens of C3H recipients bearing B6 heart allografts treated with PBS or recombinant lentivirus transduced DCs were used for analysis of T cell apoptosis signaling pathway molecules by RT-PCR. All data are representative of three separate experiments.
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Related In: Results  -  Collection


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fig7: T cells isolated on day 5 after translation from the spleens of C3H recipients bearing B6 heart allografts treated with PBS or recombinant lentivirus transduced DCs were used for analysis of T cell apoptosis signaling pathway molecules by RT-PCR. All data are representative of three separate experiments.

Mentions: To better characterize the mechanism of T cell apoptosis after costimulatory blockade, we used RT-PCR to analyze a number of apoptosis signaling pathway molecules in recipient spleens. As shown in Figure 7, a striking upregulation of Bax and GRP78 was found in recipients treated with CD80 lenti and CD86 lenti-transduced DCs compared to NC lenti-transduced DCs or PBS. These changes in endoplasmic reticulum and mitochondrial pathway were enhanced by upregulation of CHOP and suppression of Bcl-xL expression in these cells. But there were no remarkable changes in death receptor pathway among three groups.


Endoplasmic reticulum stress-mediated apoptosis involved in indirect recognition pathway blockade induces long-term heart allograft survival.

Xiang J, Gu X, Qian S, Chen Z - J. Biomed. Biotechnol. (2010)

T cells isolated on day 5 after translation from the spleens of C3H recipients bearing B6 heart allografts treated with PBS or recombinant lentivirus transduced DCs were used for analysis of T cell apoptosis signaling pathway molecules by RT-PCR. All data are representative of three separate experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2871569&req=5

fig7: T cells isolated on day 5 after translation from the spleens of C3H recipients bearing B6 heart allografts treated with PBS or recombinant lentivirus transduced DCs were used for analysis of T cell apoptosis signaling pathway molecules by RT-PCR. All data are representative of three separate experiments.
Mentions: To better characterize the mechanism of T cell apoptosis after costimulatory blockade, we used RT-PCR to analyze a number of apoptosis signaling pathway molecules in recipient spleens. As shown in Figure 7, a striking upregulation of Bax and GRP78 was found in recipients treated with CD80 lenti and CD86 lenti-transduced DCs compared to NC lenti-transduced DCs or PBS. These changes in endoplasmic reticulum and mitochondrial pathway were enhanced by upregulation of CHOP and suppression of Bcl-xL expression in these cells. But there were no remarkable changes in death receptor pathway among three groups.

Bottom Line: This approach could specifically and effectively knock down CD80 and CD86 expression.We also found a higher percentage of apoptotic T cells in lymph tissues and grafts than that detected in control group.Our results indicated that ERS-induced apoptosis may be involved in allogeneic T-cell apoptosis, and the ERS-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of allograft rejection.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.

ABSTRACT
Implementation of dendritic cell- (DC-) based therapies in organ transplantation can reduce dependency on nonspecific immunosuppression. Despite extensive research, mechanisms of equipped DCs inducing transplant tolerance remain incomplete. Here, we applied RNA interference technique to inhibit CD80 and CD86 expression in host bone marrow-derived DCs. This approach could specifically and effectively knock down CD80 and CD86 expression. T cells primed by these DCs inhibited allogeneic responses. Administration of recipient DCs loaded with alloantigen after CD80 and CD86 blockade prolonged cardiac allograft survival. We also found a higher percentage of apoptotic T cells in lymph tissues and grafts than that detected in control group. In addition, these T cells expressed high expression of GRP78 than controls, indicating activation of unfolded protein responses. Upregulation of CHOP expression among these cells suggested that the endoplasmic reticulum stress (ERS) response switched to a proapoptotic response. Our results indicated that ERS-induced apoptosis may be involved in allogeneic T-cell apoptosis, and the ERS-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of allograft rejection.

Show MeSH
Related in: MedlinePlus