Qi Z, Tufveson G, Ekberg H
Department of Experimental Research, Lund University, University Hospital, Malmö, Sweden.
Scand J Immunol. 1999 Oct;50(4):394-8. doi: 10.1046/j.1365-3083.1999.00614.x.
When applied in rodent transplant models most immunosuppressive drugs yield adequate graft protection for as long as the drug is given, and permanent graft survival is often induced. The immunomodulator, Linomide, previously shown to stimulate T cells and prevent apoptosis, usually reduces or abolishes both tolerance induction and the graft-protective effect of the immunosuppressive drug. By chance, we observed that Linomide alone exerted a modest but unequivocal graft-protective effect in the BN to WF strain combination. This finding was analysed by simple genetic mapping of rat strains. Untreated WF recipients kept BN grafts for a median of 8 days, whereas Linomide treatment prolonged graft survival to 12. 5 days (P = 0.0001). In control groups (DA to LEW, BN to LEW, DA to WF and WF to BN), median graft survival was 5.5-7 days irrespective of whether Linomide was given. However, the BN to F1 (LEW x WF) combination also manifested slightly longer graft survival in the presence of Linomide. F1 (BN x WF) to WF grafts survived a median of 15 days without Linomide and 46 days with Linomide treatment. Both in the presence and absence of Linomide, two of the control graft combinations [F1 (BN x DA) to WF and F1 (BN x WF) to BN] manifested 6-7-day graft survival. Taken together, our results suggest a delicate balance between unresponsiveness and rejection, while a single agent (Linomide) may either cause on its own long-term survival of allografts in one setting or rejection despite optimal immunosuppression in another setting.
当应用于啮齿动物移植模型时，只要给予免疫抑制药物，大多数免疫抑制药物都能提供足够的移植物保护，并且常常诱导移植物永久存活。免疫调节剂利索胺（Linomide）先前已被证明可刺激T细胞并防止细胞凋亡，通常会降低或消除免疫耐受诱导以及免疫抑制药物的移植物保护作用。偶然间，我们观察到单独使用利索胺在BN到WF品系组合中发挥了适度但明确的移植物保护作用。通过对大鼠品系进行简单的基因定位分析了这一发现。未经治疗的WF受体中BN移植物的中位存活时间为8天，而使用利索胺治疗可将移植物存活时间延长至12.5天（P = 0.0001）。在对照组（DA到LEW、BN到LEW、DA到WF以及WF到BN）中，无论是否给予利索胺，移植物的中位存活时间均为5.5 - 7天。然而，在有利索胺存在的情况下，BN到F1（LEW×WF）组合的移植物存活时间也略有延长。F1（BN×WF）到WF的移植物在未使用利索胺时的中位存活时间为15天，使用利索胺治疗时为46天。无论有无利索胺，两种对照移植物组合[F1（BN×DA）到WF和F1（BN×WF）到BN]的移植物存活时间均为6 - 7天。综上所述，我们的结果表明无反应性和排斥之间存在微妙的平衡，而单一药物（利索胺）在一种情况下可能自身导致同种异体移植物长期存活，而在另一种情况下尽管进行了最佳免疫抑制仍会导致排斥。
