ALTERATIONS OF THE INTERLEUKIN-4 PATHWAY IN PRODUCTION OF TOLERANCE BY MIXED HEMATOPOIETIC CHIMERISM
ALTERATIONS OF THE INTERLEUKIN-4 PATHWAY IN PRODUCTION OF TOLERANCE BY MIXED HEMATOPOIETIC CHIMERISM
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DOI：
10.1016/s0039-6060(05)80326-5
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发表时间：
1995-08-01
期刊：
影响因子：
3.8
通讯作者：
JORDAN, SC
中科院分区：
文献类型：
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作者：
ORLOFF, MS;DEMARA, EM;JORDAN, SC
背景诱导特异性免疫耐受可以预防血管化同种异体器官移植受者的急性和慢性排斥反应以及免疫抑制并发症。混合造血嵌合体是同种异体耐受的一种途径。在这些研究中，我们检查了混合嵌合体是否能跨越主要和次要组织相容性障碍赋予心脏移植物耐受性。我们还研究了耐受动物的同种异体移植物内和细胞培养中细胞因子基因的转录。对成年刘易斯大鼠进行致死性照射，并用50 × 10（6）个T细胞耗竭的骨髓细胞混合物进行重建。嵌合体动物接受异位供体品系和第三方心脏同种异体移植，并每天评估排斥反应。另一组嵌合体接受心脏同种异体移植，通过逆转录聚合酶链反应在不同的时间点检测细胞因子基因的转录。对照组动物中位移植物存活时间为6天。在11个混合嵌合体中，craft存活时间从超过165天到超过274天不等（P < 0.001），并且没有观察到排斥反应或移植物抗宿主病的发生。细胞因子转录检测显示体内和体外白细胞介素-4转录的显著变化。细胞因子基因转录的改变描述了该模型中的耐受性。混合嵌合体使心脏移植物长期无反应，跨越主要和次要的组织相容性障碍，具有理想的临床应用特征。
Background. The induction of specific tolerance could prevent acute and chronic rejection, as well as immunosuppressive complications, in recipients of vascularized organ allografts. Mixed hematopoietic chimerism is one approach to allogeneic tolerance. In these studies we examined whether mixed chimerism can confer tolerance to heart allografts across major and minor histocompatibility barriers. We also examined the transcription of cytokine genes within the allografts of tolerant animals and in cell culture .Methods. Adult Lewis rats were lethally irradiated and reconstituted with a mixture of 50 x 10(6) T-cell depleted bone marrow cells. Chimeric animals received heterotopic donor strain and third-party heart allografts and were assessed daily for rejection. Another set of chimeras received heart allografts that were examined at varying time points for transcription of cytokine genes by reverse-transcriptase polymerase chain reaction.Results. Median graft survival in control animals was 6 days. craft survival in 11 mixed chimeras ranged from more than 165 to more than 274 days (p < 0.001), and no episode of rejection or graft-versus-host disease was observed. Examination of cytokine transcriptions revealed dramatic alterations in interleukin-4 transcription in vivo and in vitro.Conclusions. Alterations in cytokine gene transcription are descriptive of tolerance in this model. Mixed chimerism confers long-term unresponsiveness to heart allografts across major and minor histocompatibility barriers with desirable features clinical application.