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猪-猴模型心脏异种移植中补体的激活以及胸腺内接种异种抗原联合全身γ射线照射的影响。

Activation of complement in the discordant heart xenotransplantation of pig-to-monkey model and the impact of intrathymic inoculation of xenogeneic antigen combined with whole-body gamma-radiation.

作者信息

Qv J, Chen G, Shen Z, Jiang G, Ding J, Gao W, Chen C

机构信息

Department of Thoracic Surgery, ShangHai Pulmonary hospital, TongJi University, ShangHai, China.

出版信息

Transplant Proc. 2009 Nov;41(9):3905-8. doi: 10.1016/j.transproceed.2009.05.038.

DOI:10.1016/j.transproceed.2009.05.038
PMID:19917409
Abstract

OBJECTIVE

This study investigated changes in complement in discordant heart xenotransplantation using a pig-to-monkey model as well as the impact of intrathymic inoculation (IT) with xenogeneic antigen combined with whole-body gamma-radiation (WBI).

METHODS

In this experiment, pigs and monkeys selected as donors and recipients, respectively, were randomly divided into three groups: a blank group (group A), a whole-body irradiation group (group B) and an irradiation plus intrathymic injection group (group C). In every group, monkeys underwent heterotopic heart xenotransplantation.

RESULTS

The results showed that the survival of donor hearts in group C was significantly longer than that of group A (P < .01). In mixed lymphocyte reactions, there was a significant reduction of the stimulation index in group C compared with group A. After xenotransplantation, the level of xenoreactive antibody in group C rose slower than that in group A or group B (P < .01). After rejection, the levels of CD46 and C3 declined greatly.

CONCLUSIONS

These results suggested that pretreatment with IT and WBI induced T-cell immunosuppression, restraining elicited xenoreactive antibody production of both immunoglobulin M and immunoglobulin G classes. However, it did not hinder complement activation via the classical pathway during hyperacute rejection and consequent xenograft rejection.

摘要

目的

本研究利用猪到猴的模型，研究不协调性心脏异种移植中补体的变化，以及胸腺内接种（IT）异种抗原联合全身γ射线照射（WBI）的影响。

方法

在本实验中，分别选作供体和受体的猪和猴被随机分为三组：空白组（A组）、全身照射组（B组）和照射加胸腺内注射组（C组）。每组中的猴子均接受异位心脏异种移植。

结果

结果显示，C组供体心脏的存活时间显著长于A组（P <.01）。在混合淋巴细胞反应中，与A组相比，C组的刺激指数显著降低。异种移植后，C组中异种反应性抗体水平的上升速度慢于A组或B组（P <.01）。排斥反应后，CD46和C3水平大幅下降。

结论

这些结果表明，IT和WBI预处理诱导了T细胞免疫抑制，抑制了免疫球蛋白M和免疫球蛋白G类异种反应性抗体的产生。然而，它并未阻碍超急性排斥反应及随后的异种移植物排斥反应期间通过经典途径的补体激活。