Localized interleukin-10 gene transfer induces apoptosis of alloreactive T cells via FAS/FASL pathway, improves function, and prolongs survival of cardiac allograft
Localized interleukin-10 gene transfer induces apoptosis of alloreactive T cells via FAS/FASL pathway, improves function, and prolongs survival of cardiac allograft
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局部白细胞介素10基因转移通过FAS/FASL途径诱导同种异体反应性T细胞凋亡，改善功能并延长同种异体心脏移植物的存活
DOI：
10.1097/00007890-200204150-00002
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发表时间：
2002
期刊：
影响因子：
6.2
通讯作者：
H. Laks
中科院分区：
文献类型：
--
作者：
K. Oshima;L. Sen;G. Cui;T. Tung;B. M. Sacks;Anthony Arellano;H. Laks
我们假设局部IL-10基因转移可以诱导同种异体反应性T细胞凋亡，并使用家兔异位同种异体心脏移植模型，通过脂质体介导的离体冠状动脉内IL-10基因转移来验证这一假设。局部IL-10过表达延长心脏移植物存活超过3倍。与IL-10过度表达的时间进程相平行，术后第3-6天基因治疗组凋亡的CD 3+细胞占总CD 3+细胞的百分比（36.5±3.9%）明显高于对照组（6.2± 2.6%），P <0.01，术后第7 ~ 10天进一步升高（45.8±5.7%）。CD 4+、CD 8+细胞凋亡率在基因组也明显升高（P <0.01）。与此相反，在POD 7 -10，心肌细胞凋亡率由对照组的10.1±0.8%降至基因组的3.5±0.4%（P <0.01）。CD 4+、CD 8+细胞凋亡率的升高与CD 4+、CD 8+细胞凋亡率的降低呈负相关（P <0.01）。Caspase-3阳性细胞百分率在基因组显著降低，而Caspase-3阳性细胞百分率在基因组显著升高（P <0.01）。凋亡T淋巴细胞Fas表达率在基因组为60-80%，对照组为10%以下（P <0.01）。这些结果表明，局部IL-10基因转移诱导同种异体反应性T细胞凋亡，通过Fas/FasL途径，可能有助于减轻急性排斥反应，改善心脏功能，并在IL-10基因治疗的心脏移植物的生存期延长。
We hypothesized that localized IL-10 gene transfer can induce alloreactive T cell apoptosis and tested this hypothesis with liposome-mediated ex vivo intracoronary IL-10 gene transfer using a functional heterotopic allograft heart transplant model in rabbits. Localized IL-10 overexpression prolonged cardiac allograft survival over three folds. In parallel with the time-course of IL-10 overexpression, the percentage of apoptotic CD3+ cells among total CD3+ cells was significantly increased in the gene therapy group (36.5±3.9%) compared with that in the control group (6.2±2.6%, P <0.01) on postoperative day (POD) 3–6, and it was further increased (45.8±5.7%) on POD7–10. Apoptotic CD4+ and CD8+ cells were also significantly increased in the gene group (P <0.01). In contrast, the percentage of apoptotic myocytes significantly decreased from 10.1±0.8% in the control group to 3.5±0.4% in the gene group on POD7–10 (P <0.01). This reduction was inversely correlated with the increase in the percentages of apoptotic CD4+ and CD8+ cells (P <0.01). The percentage of caspase-3 positive myocytes was significantly reduced, although percentages of caspase-3 positive CD4+ and CD8+ cells were markedly increased in the gene group (P <0.01). Moreover, about 60–80% of apoptotic T lymphocytes expressed Fas in the gene group compared with less than 10% in the control group (P <0.01). These results suggest that localized IL-10 gene transfer induces alloreactive T cell apoptosis via the Fas/FasL pathway that may contribute to the alleviated acute rejection, improved cardiac function, and prolonged survival in the IL-10 gene-treated cardiac allografts.
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影响因子：
4.4
作者：
S. Qian;Una Lu;F. Fu;Youping Li;Wei Li;T. Starzl;J. Fung;A. Thomson
通讯作者：
S. Qian;Una Lu;F. Fu;Youping Li;Wei Li;T. Starzl;J. Fung;A. Thomson
影响因子：
4.4
作者：
A. Chernoff;E. Granowitz;L. Shapiro;E. Vannier;G. Lonnemann;J. Angel;J. Kennedy;A. Rabson;S. Wolff;C. Dinarello
通讯作者：
A. Chernoff;E. Granowitz;L. Shapiro;E. Vannier;G. Lonnemann;J. Angel;J. Kennedy;A. Rabson;S. Wolff;C. Dinarello
全身给予细胞白细胞介素 10 会加剧小鼠心脏同种异体移植排斥反应。
影响因子：
6.2
作者：
Qian,S;Li,W;Li,Y;Fu,F;Lu,L;Fung,JJ;Thomson,AW
通讯作者：
Thomson,AW
小鼠心脏移植物中的细胞凋亡。
影响因子：
6.2
作者：
Bergese,SD;Klenotic,SM;Wakely,ME;Sedmak,DD;Orosz,CG
通讯作者：
Orosz,CG
逆转录病毒介导的病毒 IL-10 基因转移可延长小鼠同种异体心脏移植物的存活时间。
DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Qin,L;Chavin,KD;Ding,Y;Tahara,H;Favaro,JP;Woodward,JE;Suzuki,T;Robbins,PD;Lotze,MT;Bromberg,JS
通讯作者：
Bromberg,JS