Ghobrial R, Karczewski M, Ferraresso M, Tian L, Stepkowski S M, Kahan B D
Department of Surgery, University of Texas Medical School-Houston, USA.
Ann Transplant. 1996;1(4):22-9.
The purpose of the study presented herein was to examine immune performances of rat heart allograft recipients immunosuppressed with sirolimus (SRL, rapamycin; Rapamune, Wyeth-Ayerst, Princeton, NJ).
The immune performances of lymphocytes harvested from SRL-treated Wistar Furth (WF; RT1u) recipients of Buffalo (BUF; RT1b) heart allografts were examined on days 7, 14, and 90 postgrafting.
Whether derived from normal WF rats, SRL-treated WF heart recipients, or SRL-untreated WF heart recipients, pan-T cell population purified from the lymph nodes or spleens on day 7 or 14 displayed similar responses to phytohemaglutinin, anti-T cell receptor R73 monoclonal antibody, donor-type BUF, or third-party Brown Norway alloantigenic stimulators. There was no in vitro evidence of suppressor T cells in SRL-treated recipients. The frequencies of anti-BUF-specific cytotoxic T cells, as shown by limiting dilution analysis, were similar in the short- (days 7 or 14) and in the long- (day 90) term surviving recipients. SRL treatment did not affect the expression of interleukin-2 (IL-2) messenger RNA (mRNA) by T helper 1 (Th1) or of IL-4 and IL-10 mRNA by Th2 cells on days 7 and 14 postgrafting, but did induce selective activation of Th2 cells on day 60 postgrafting. Administration of SRL induced the production of non-complement (C')-fixing IgG2c BUF-specific alloantibodies that appeared in the sera of unresponsive recipients on day 14 postgrafting and reached a peak concentration on day 120 postgrafting. In contrast to untreated recipients that rejected BUF heart allografts, all SRL-treated WF recipients failed to produce C'-fixing BUF-specific alloantibodies.
SRL promotes long-term selective activation of Th2 cells and the production of non-C'-fixing IgG2c blocking antibodies.
本文所呈现研究的目的是检测接受西罗莫司（SRL，雷帕霉素；雷帕鸣，惠氏-艾尔斯特，新泽西州普林斯顿）免疫抑制的大鼠心脏同种异体移植受者的免疫性能。
在移植后第7、14和90天，检测从接受SRL治疗的布法罗（BUF；RT1b）心脏同种异体移植的Wistar Furth（WF；RT1u）受者采集的淋巴细胞的免疫性能。
无论来源于正常WF大鼠、接受SRL治疗的WF心脏受者还是未接受SRL治疗的WF心脏受者，在第7天或第14天从淋巴结或脾脏中纯化的全T细胞群体对植物血凝素、抗T细胞受体R73单克隆抗体、供体类型BUF或第三方棕色挪威同种异体抗原刺激物表现出相似的反应。在接受SRL治疗的受者中没有体外证据表明存在抑制性T细胞。通过有限稀释分析显示，短期（第7天或第14天）和长期（第90天）存活的受者中抗BUF特异性细胞毒性T细胞的频率相似。SRL治疗在移植后第7天和第14天不影响辅助性T细胞1（Th1）的白细胞介素-2（IL-2）信使核糖核酸（mRNA）表达或Th2细胞的IL-4和IL-10 mRNA表达，但在移植后第60天确实诱导了Th2细胞的选择性活化。给予SRL诱导产生非补体（C'）结合的IgG2c BUF特异性同种异体抗体，这些抗体在移植后第14天出现在无反应受者的血清中，并在移植后第120天达到峰值浓度。与排斥BUF心脏同种异体移植的未治疗受者相反，所有接受SRL治疗的WF受者均未产生C'结合的BUF特异性同种异体抗体。
SRL促进Th2细胞的长期选择性活化和非C'结合的IgG2c封闭抗体的产生。
