The effects of perioperative portal venous inoculation with donor lymphocytes on allograft survival in the rat.

在大鼠系统中检测了围手术期门静脉接种供者淋巴细胞对移植肾存活的影响。未经治疗的Lewis宿主在7.8±0.6天内排斥BN肾移植。第0天静脉注射1x10 BN细胞可轻微延长移植肾存活时间(MST=9.5±3.0天)，而第0天静脉注射1×10 BN细胞可显著延长移植肾存活时间至22.2±5.3天(p0.01)。移植物存活的延长是抗原特异性的。当PV处理的LEW宿主的血清以总体积的3%加入MLC时，它对MLC对BN细胞的反应抑制了71%，但对第三方DA刺激物的MLC反应没有抑制。BN肾移植后移植肾存活时间从7.8天延长至18.9±5.5天，但不能延长第三方DA移植肾存活时间(MST=7.5±0.6天)。在持续排斥反应中，耐受宿主经丝裂原刺激后的移植物浸润性细胞(GIC)体外细胞因子产量(IL-2：8.7±1.4U/ml，IL-3：15.4±0.6U/ml，IL-6：24.6±3.5U/ml)明显低于未接种对照宿主(IL-2：19.6±2.9U/ml，IL-3：22.2±2.7U/ml，IL-6：67.5±13.2U/ml)。在移植后第6天，接种PVLEW宿主的GIC细胞中细胞毒/抑制性T细胞(OX-8)和Ia阳性细胞(OX-6)的百分比(分别为23.1±4.4%和9.0±2.0%)显著低于未接种的对照组(分别为39.4±8.2%和23.0±1.9%)。在持续排斥期间，耐受宿主的GIC对供者胚样淋巴细胞的杀伤活性(19.0±1.2%)显著低于对照移植物(51.5±5.3%)。这些结果表明，经门静脉注入供者淋巴细胞后，移植肾中Th和TC细胞的活化均受到原位抑制。

Effects of perioperative portal venous inoculation of donor lymphocytes on renal allograft survival were tested in rat system. Untreated Lewis hosts rejected BN renal grafts at 7.8+0.6 days. IV administration of 1x10 BN cells to LEW hosts on day 0 caused a slight, but not significant prolongation of renal graft survival(MST=9.5+3.0 days), whereas PV inoculation of 1x10 BN cells on day 0 remarkably prolonged renal graft survival to 22.2+5.3 days(p 0.01). The prolongation of the graft survival was antigen-specific. When serum from PV-treated LEW hosts was added to MLC at a concentration of 3% of total volume, it suppressed the MLC reaction toward BN cells by 71%, but not toward third-party DA stimulators. Adoptive transfer of the serum into the virgin secondary LEW hosts significantly prolonged the graft survival of BN kidney from 7.8 to 18.9+5.5 days, but not third-party DA graft survivals(MST=7.5+0.6 days). The amounts of in vitro cytokine production of graft-infiltrating-cells(GIC) from tolerant hosts after mitogen stimulation were remarkably decreased(IL-2:8.7+1.4 U/ml, IL-3:15.4+0.6U/ml, and IL-6:24.6+3.5 U/ml) than those of uninoculated control hosts during ongoing rejection(IL-2:19.6+2.9 U/ml, IL-3:22.2+2.7 U/ml, and IL-6:67.5+13.2U/ml). The percentage of cytotoxic/suppressor T cells(OX-8) and Ia-positive cells(OX-6) in GIC cells(23.1+4.4% and 9.0+2.0%, respectively) from PV inoculated LEW hosts on day 6 postgrafting were significantly lower than those of uninoculated control recipients(39.4+8.2% and 23.0+1.9%, respectively). Cytolytic activity of GIC from tolerant hosts toward donor blastoid lymphocytes was significantly decreased(19.0+1.2%), compared with that from control allografts during ongoing rejection(51.5+5.3%). These results demonstrated that activation of both Th and Tc cells was inhibited in situ in renal allograft following administration of donor lymphocytes through the portal vein.