Thai N L, Fu F, Qian S, Sun H, Gao L, Wang S C, Demetris A J, Woo J, Thomson A W, Duquesnoy R J
Pittsburgh Transplantation Institute, University of Pittsburgh School of Medicine, Pennsylvania 15213.
Transplantation. 1995 Jan 27;59(2):274-81.
Although mouse liver allografts are spontaneously accepted without immunosuppression in many strain combinations, rejection can be induced by presensitization with a donor skin graft two weeks prior to transplantation. In this study, the semiquantitative reverse transcription polymerase chain reaction (RTPCR) was used to assess the involvement of T helper (TH) cell subsets in liver allograft acceptance by determining cytokine mRNA in the graft and spleen of recipients with (A) spontaneously accepting allografts (B) rejecting liver allografts after previous skin sensitization, and (C) syngeneic controls. Spontaneously accepted liver allografts showed upregulation of TH1 (IL-2, IFN-gamma) and TH2 (IL-4, IL-10) intragraft cytokine mRNA, which peaked at day 6 and tapered off thereafter, when compared with levels in syngeneic grafts, but both IFN-gamma and IL-10 mRNA persisted up to day 30. This cytokine mRNA profile correlated with the transient intragraft inflammation associated with spontaneously resolving rejection. Presensitized recipients that rejected their grafts revealed marked upregulation of TH1 (IL-2 and IFN-gamma) and TH2 (IL-4, IL-6) intragraft cytokine mRNAs compared with spontaneously accepting recipients, although IL-10 mRNA levels showed no differences between the two groups. The most striking difference was seen in IFN-gamma levels, which correlated well with the preferential deposition of IgG2a antibody isotype in the rejecting compared with the spontaneously accepting liver allograft recipients. These results suggested an association between liver allograft rejection and enhanced TH1 cytokine immune response. The ability to reject liver allografts by the adoptive transfer of splenocytes, but not serum, from a sensitized mouse ruled out preformed antibodies alone as a cause of rejection. However, spleen cytokine mRNA profiles showed no differences or trends in TH1 or TH2 expression in spontaneously accepting versus rejecting recipients, which suggested that the spleen is not a major site of alloreactive immune expansion. These data suggest that spontaneous acceptance of mouse liver allografts is associated with an insufficient intragraft TH1 cytokine response, the cause of which is currently under investigation.
尽管在许多品系组合中，小鼠肝脏同种异体移植在没有免疫抑制的情况下能被自发接受，但在移植前两周用供体皮肤移植进行预致敏可诱导排斥反应。在本研究中，采用半定量逆转录聚合酶链反应（RTPCR），通过测定（A）自发接受同种异体移植的、（B）先前皮肤致敏后排斥肝脏同种异体移植的以及（C）同基因对照受体的移植物和脾脏中的细胞因子mRNA，来评估T辅助（TH）细胞亚群在肝脏同种异体移植接受过程中的参与情况。与同基因移植物相比，自发接受的肝脏同种异体移植显示移植物内TH1（IL-2、IFN-γ）和TH2（IL-4、IL-10）细胞因子mRNA上调，在第6天达到峰值，此后逐渐下降，但IFN-γ和IL-10 mRNA一直持续到第30天。这种细胞因子mRNA谱与与自发消退的排斥反应相关的短暂移植物内炎症相关。与自发接受移植的受体相比，排斥移植物的预致敏受体显示移植物内TH1（IL-2和IFN-γ）和TH2（IL-4、IL-6）细胞因子mRNA显著上调，尽管两组间IL-10 mRNA水平无差异。最显著的差异见于IFN-γ水平，与自发接受肝脏同种异体移植的受体相比，其与排斥反应中IgG2a抗体同种型的优先沉积密切相关。这些结果提示肝脏同种异体移植排斥与增强的TH1细胞因子免疫反应之间存在关联。通过转输致敏小鼠的脾细胞而非血清来排斥肝脏同种异体移植的能力排除了仅预先形成的抗体作为排斥原因的可能性。然而，脾脏细胞因子mRNA谱在自发接受与排斥的受体中TH1或TH2表达方面未显示差异或趋势，这表明脾脏不是同种异体反应性免疫扩增的主要部位。这些数据表明，小鼠肝脏同种异体移植的自发接受与移植物内TH1细胞因子反应不足有关，其原因目前正在研究中。
