Baan C C, Metselaar H J, Mol W M, Tilanus H W, IJermans J M, Zondervan P E, Schalm S W, Niesters H G, Weimar W
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Clin Transplant. 1996 Dec;10(6 Pt 1):542-9.
The mechanism underlying spontaneously resolving allograft rejection following clinical liver transplantation is unidentified. In this process, immunoregulatory T helper (Th)-2 cytokines like IL-4, often identified with down-regulation of the Th1-dependent (IL-2) cell-mediated response, might play a significant but unknown role. For this reason, we analyzed mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in 57 biopsies derived from 19 recipients. Specimens included biopsies without evidence of rejection (n = 36), biopsies with histological evidence of rejection (n = 10) not followed by clinical signs of graft rejection, and biopsies with histological rejection that were accompanied with clinical rejection (n = 11), defined by rising serum bilirubin and aspartate amino transaminase (ASAT) levels. Intragraft IL-4 mRNA expression significantly correlated with spontaneously resolving rejections. In 70% (7/10) of these biopsies, IL-4 mRNA was detectable, while only 19% (7/36) of the biopsies without signs of rejection (p < 0.01; Fisher's exact test) and 18% (2/11) of the rejection biopsies concurrent with graft dysfunction expressed the IL-4 gene (p = 0.03). In contrast, IL-2 mRNA expression was not detectable in biopsies derived from the spontaneously resolving rejections. None (0/10) of these samples expressed the IL-2 gene, which was not significantly different from the proportion of biopsies transcribing the IL-2 gene in the absence of rejection (11%, 4/36). IL-2 mRNA expression was found more often in biopsies associated with graft dysfunction (36%, 4/11). These results show that IL-4, in contrast to IL-2 mRNA expression, is associated with spontaneously resolving liver rejection. This suggests that Th2 cells down-regulate the Th1-dependent cell-mediated immune response after clinical liver transplantation.
临床肝移植后同种异体移植物排斥反应自然缓解的潜在机制尚不清楚。在这个过程中，免疫调节性辅助性T（Th）-2细胞因子如白细胞介素（IL）-4，通常与Th1依赖性（IL-2）细胞介导反应的下调有关，可能发挥着重要但未知的作用。因此，我们通过逆转录聚合酶链反应（RT-PCR）分析了来自19名受者的57份活检组织中的mRNA表达。样本包括无排斥反应证据的活检组织（n = 36）、有组织学排斥反应证据但无移植排斥临床体征的活检组织（n = 10）以及伴有临床排斥反应（根据血清胆红素和天冬氨酸氨基转氨酶（ASAT）水平升高定义）的组织学排斥活检组织（n = 11）。移植物内IL-4 mRNA表达与排斥反应自然缓解显著相关。在这些活检组织中，70%（7/10）可检测到IL-4 mRNA，而无排斥反应迹象的活检组织中只有19%（7/36）（p < 0.01；Fisher精确检验），与移植功能障碍同时发生的排斥活检组织中有18%（2/11）表达IL-4基因（p = 0.03）。相反，在排斥反应自然缓解的活检组织中未检测到IL-2 mRNA表达。这些样本中无一（0/10）表达IL-2基因，这与无排斥反应时转录IL-2基因的活检组织比例（11%，4/36）无显著差异。在与移植功能障碍相关的活检组织中更常发现IL-2 mRNA表达（36%，4/11）。这些结果表明，与IL-2 mRNA表达相反，IL-4与肝移植排斥反应的自然缓解有关。这表明Th2细胞在临床肝移植后下调Th1依赖性细胞介导的免疫反应。
