Alexander D Z, Pearson T C, Hendrix R, Ritchie S C, Larsen C P
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Transpl Immunol. 1996 Mar;4(1):46-8. doi: 10.1016/s0966-3274(96)80033-5.
Multiple effector cells have been implicated in transplant rejection, including cytotoxic T cells, B cells, macrophages and NK cells. The purpose of this study was to examine the effector pathways which are critical to murine cardiac allograft rejection. RT-PCR (reverse transcriptase-polymerase chain reaction) analysis of syngeneic and allogeneic vascularized heterotopic cardiac grafts at 5, 8 and 12 days following transplantation demonstrate constitutive expression of Fas in both the syngeneic and allogeneic grafts as well as in normal heart. However, FasL, granzyme, and perforin expression were shown to be up-regulated on days 5-12 in the allograft with no expression in syngeneic grafts or in normal hearts. We have recently analyzed the functional significance of T cell cytotoxic pathways and found that neither the Fas nor CD8+ cytotoxic pathways are required for murine cardiac allograft rejection. In light of these results, we investigated the functional significance of other effector cells in the rejection process. B cell deficient C57BL/10-IgHtm1Cgn mice rejected cardiac allografts from normal donors at control rate. Finally, RT-PCR was used to analyze the expression of macrophage effector transcripts in allograft rejection. Transcripts for iNOS (inducible nitric oxide synthase) and TNF alpha (tumor necrosis factor-alpha) were up-regulated on days 5-12 in untreated allografts with undetectable expression in normal heart or syngeneic grafts. These results demonstrate that effective allograft rejection can occur in the absence of B cells and T cell cytotoxicity pathways suggesting that other effector pathways, such as delayed-type hypersensitivity responses by macrophages, may be critical for allograft rejection.
多种效应细胞与移植排斥反应有关，包括细胞毒性T细胞、B细胞、巨噬细胞和自然杀伤细胞。本研究的目的是检测对小鼠心脏同种异体移植排斥反应至关重要的效应途径。对移植后5天、8天和12天的同基因和异基因血管化异位心脏移植物进行逆转录聚合酶链反应（RT-PCR）分析，结果显示Fas在同基因和异基因移植物以及正常心脏中均有组成性表达。然而，FasL、颗粒酶和穿孔素的表达在同种异体移植物中于第5 - 12天被上调，而同基因移植物或正常心脏中无表达。我们最近分析了T细胞细胞毒性途径的功能意义，发现Fas和CD8 +细胞毒性途径都不是小鼠心脏同种异体移植排斥反应所必需的。鉴于这些结果，我们研究了其他效应细胞在排斥过程中的功能意义。B细胞缺陷的C57BL/10-IgHtm1Cgn小鼠以对照速率排斥来自正常供体的心脏同种异体移植物。最后，使用RT-PCR分析同种异体移植排斥反应中巨噬细胞效应转录本的表达。未经处理的同种异体移植物中，诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子-α（TNFα）的转录本在第5 - 12天被上调，而正常心脏或同基因移植物中未检测到表达。这些结果表明，在没有B细胞和T细胞细胞毒性途径的情况下也可发生有效的同种异体移植排斥反应，这表明其他效应途径，如巨噬细胞介导的迟发型超敏反应，可能对同种异体移植排斥反应至关重要。
