Sun J, McCaughan G W, Matsumoto Y, Sheil A G, Gallagher N D, Bishop G A
Department of Transplantation Surgery, Sydney University, New South Wales, Australia.
Transplantation. 1994 May 15;57(9):1349-57.
Liver allografts in the fully allogenic combination of LEW donor liver to DA recipient (LEW-->DA) are spontaneously tolerated (TOL) with no requirement for immunosuppression, while DA-->LEW allografts are rejected in 12-15 days (REJ). We investigated the mechanism of tolerance induction by identifying differences between TOL and REJ grafts from day 1 to day 9 after transplantation and in normal livers and syngeneic liver graft controls. Infiltrating cell populations were counted after immunohistochemical staining of liver graft sections. There were occasional minor differences between TOL and REJ grafts in the T cell or CD11b/c+ (monocyte/macrophage/granulocyte) infiltrate. In contrast, there was a major difference in B cell infiltrate between TOL and REJ liver grafts. Membrane IgD+ cells were significantly greater in TOL (1796 +/- 225) versus REJ (569 +/- 281) (P = 0.004) portal tracts, as were B220+ cells (1086 +/- 100 vs. 181 +/- 105, P = 0.0004) and CD45RC+ cells (2317 +/- 456 vs. 597 +/- 194, P = 0.004). IgG1, IgG2a, IgM, and IgD deposition in liver allografts, identified by immunohistochemical staining of tissue sections, revealed no IgG or IgD in normal rat liver and low levels of IgM. Deposition of IgG1 was observed in REJ but not in TOL liver on days 7 and 9. IgM was increased in both TOL and REJ liver and appeared to be associated mainly with hepatocytes in REJ and with infiltrate in TOL liver. There was a parallel increase in IgG1-expressing plasma cells in the spleen and lymph nodes of REJ but not TOL animals. Cytokine mRNA was analyzed by reverse transcription and semiquantitative polymerase chain reaction amplification of liver RNA. Increased levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, transforming growth factor-beta, and IFN-gamma were observed, with similar levels of expression in TOL compared with REJ liver. Cytokine mRNA in syngeneic grafts was not different from normal except for IL-6 and transforming growth factor-beta, which were increased. There is no major difference in the T cell component of the infiltrate or in the extent of upregulation of cytokine mRNA between TOL and REJ grafts. There is a major difference in the B cell compartment, with more B cells in TOL livers and deposition of IgG1 in REJ grafts.
在将LEW供体肝脏移植给DA受体的完全同种异体组合（LEW→DA）中，肝脏同种异体移植物可自发耐受（TOL），无需免疫抑制，而DA→LEW同种异体移植物在12 - 15天内被排斥（REJ）。我们通过识别移植后第1天至第9天TOL和REJ移植物之间以及正常肝脏和同基因肝脏移植物对照之间的差异，研究了耐受诱导的机制。对肝脏移植物切片进行免疫组织化学染色后，对浸润细胞群体进行计数。在T细胞或CD11b/c +（单核细胞/巨噬细胞/粒细胞）浸润方面，TOL和REJ移植物之间偶尔存在微小差异。相比之下，TOL和REJ肝脏移植物在B细胞浸润方面存在重大差异。在TOL（1796±225）与REJ（569±281）（P = 0.004）的门静脉区域中，膜IgD +细胞显著更多，B220 +细胞也是如此（1086±100对181±105，P = 0.0004）以及CD45RC +细胞（2317±456对597±194，P = 0.004）。通过组织切片的免疫组织化学染色鉴定，肝脏同种异体移植物中的IgG1、IgG2a、IgM和IgD沉积显示正常大鼠肝脏中没有IgG或IgD，IgM水平较低。在第7天和第9天，在REJ肝脏中观察到IgG1沉积，但在TOL肝脏中未观察到。在TOL和REJ肝脏中IgM均增加，并且在REJ中似乎主要与肝细胞相关，在TOL肝脏中与浸润相关。在REJ动物而非TOL动物的脾脏和淋巴结中，表达IgG1的浆细胞有平行增加。通过逆转录和肝脏RNA的半定量聚合酶链反应扩增分析细胞因子mRNA。观察到IL - 2、IL - 4、IL - 6、IL - 10、TNF -α、转化生长因子 -β和IFN -γ水平升高，TOL肝脏与REJ肝脏中的表达水平相似。同基因移植物中的细胞因子mRNA与正常情况没有差异，除了IL - 6和转化生长因子 -β增加。在浸润的T细胞成分或细胞因子mRNA上调程度方面，TOL和REJ移植物之间没有重大差异。在B细胞区室存在重大差异，TOL肝脏中有更多B细胞，而REJ移植物中有IgG1沉积。
