心脏同种异体移植中病毒白细胞介素-10的高水平表达未能延长移植物存活时间。

High-level expression of viral interleukin-10 in cardiac allografts fails to prolong graft survival.

作者信息

Adachi Osamu, Yamato Eiji, Kawamoto Shunsuke, Yamamoto Mayu, Tahara Hideaki, Tabayashi Koichi, Miyazaki Jun-Ichi

机构信息

Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Transplantation. 2002 Dec 15;74(11):1603-8. doi: 10.1097/00007890-200212150-00019.

DOI:10.1097/00007890-200212150-00019

PMID:12490795

Abstract

BACKGROUND

Viral interleukin (vIL)-10, encoded in the Epstein-Barr virus genome, shares many of the anti-inflammatory properties of cellular IL-10 but is supposed to lack IL-10's immunostimulatory properties. Thus, vIL-10 is expected to offer superior immunosuppression.

METHODS

We established transgenic mice (vIL-10 Tg) that express vIL-10 systemically and transplanted their hearts as vascularized allografts into unmodified major histocompatibility complex (MHC) full-mismatch or MHC class II-disparate mice.

RESULTS

The vIL-10 Tg mice revealed high-level expression of vIL-10 in major organs including the heart. However, the heart grafts from the vIL-10 Tg mice failed to exhibit prolonged survival in combination with either the MHC full-mismatch or the class II-disparate mice. In the MHC class II-disparate mice, the vIL-10 Tg heart grafts showed severe CD8 T-cell infiltration and increased interferon (IFN)-gamma mRNA expression compared with non-Tg grafts.

CONCLUSION

High level expression of vIL-10 in grafts can exacerbate immunological rejection in an allogenic transplantation model.

摘要

背景

病毒白细胞介素（vIL）-10由爱泼斯坦-巴尔病毒基因组编码，具有许多细胞IL-10的抗炎特性，但被认为缺乏IL-10的免疫刺激特性。因此，vIL-10有望提供更强的免疫抑制作用。

方法

我们建立了全身表达vIL-10的转基因小鼠（vIL-10 Tg），并将其心脏作为血管化同种异体移植物移植到未修饰的主要组织相容性复合体（MHC）完全不匹配或MHC II类不同的小鼠体内。

结果

vIL-10 Tg小鼠在包括心脏在内的主要器官中显示出vIL-10的高水平表达。然而，来自vIL-10 Tg小鼠的心脏移植物与MHC完全不匹配或II类不同的小鼠联合时，未能表现出延长的存活时间。在MHC II类不同的小鼠中，与非Tg移植物相比，vIL-10 Tg心脏移植物显示出严重的CD8 T细胞浸润和干扰素（IFN）-γ mRNA表达增加。