Oluwole S F, Tezuka K, Wasfie T, Stegall M D, Reemtsma K, Hardy M A
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Transplantation. 1989 Nov;48(5):751-5.
The role of humoral immunity in graft rejection in the rat model remains controversial. Passive transfer of cytotoxic alloantibody (CAA) has resulted either in hyperacute rejection or in graft enhancement. This study examines the effect of transfer of CAA on cardiac allograft survival in three rat strain combinations that are fully mismatched at the major histocompatibility (MHC) loci. Strain-specific immune responsiveness in donor-recipient pairs varied from low (Lewis-to-ACI) to high (ACI-to-Lewis) as measured by mixed lymphocyte reactions. CAA was obtained from rats sensitized by three successive skin grafts at weekly intervals. Group 1 (high responder recipients), which consisted of Lewis rats presensitized to ACI and had a lymphocytotoxicity titer of 1:512 to 1:2048, rejected ACI cardiac allografts in 10.8 +/- 7.2 hr compared with 6.5 +/- 0.5 days in naive controls (p less than 0.001). Injection of 1 ml of high-titer CAA into naive Lewis rats immediately after ACI cardiac grafting led to hyperacute rejection of ACI hears in 2.1 +/- 0.8 hr while 1 ml of CAA followed by 2 ml of guinea pig complement (GPC) resulted in even faster rejection (mean survival time (MST) of 23.8 +/- 4.7 min). Injection of 2 ml GPC alone or in combination with 1 ml naive Lewis serum had no effect on graft survival. Multiple pretransplant injections of 1 ml of CAA on days -3, -2,-1, and 0 relative to transplantation resulted in significant prolongation of allograft survival (MST of 10.3 +/- 0.3 days; P less than 0.01). In group 2 (intermediate responder recipients), where Lewis rats were presensitized to WF strain and where cytotoxicity titer was 1:16 to 1:256, the recipients rejected WF hearts in 23.8 +/- 5.8 hr compared with 6.8 +/- 0.8 days in unsensitized control recipients (P less than 0.001). Injection of 1 ml of Lewis anti-WF CAA resulted in prolonged graft survival of 9.7 +/- 3.5 days, while injection of 1 ml of CAA followed by 2 ml of GPC caused hyperacute rejection in 104 +/- 61.7 min. Pretransplant injections of CAA on days -3, -2, -1, and 0 resulted in enhancement, with an MST of 16.3 +/- 1.3 days (P less than 0.001). In group 3 (low responder recipients), ACI presensitized to Lewis developed a cytotoxicity titer of 1:2 to 1:32 and rejected Lewis hearts in 5.3 +/- 0.4 days compared with 10.6 +/- 1.0 days in naive recipients.(ABSTRACT TRUNCATED AT 400 WORDS)
在大鼠模型中，体液免疫在移植排斥反应中的作用仍存在争议。细胞毒性同种异体抗体（CAA）的被动转移可导致超急性排斥反应或移植增强。本研究检测了CAA转移对三种大鼠品系组合心脏同种异体移植存活的影响，这三种组合在主要组织相容性（MHC）位点完全不匹配。通过混合淋巴细胞反应测定，供体 - 受体对中的品系特异性免疫反应性从低（Lewis到ACI）到高（ACI到Lewis）不等。CAA取自每周接受三次连续皮肤移植致敏的大鼠。第1组（高反应性受体）由预先对ACI致敏的Lewis大鼠组成，其淋巴细胞毒性滴度为1:512至1:2048，与未致敏的对照相比，在10.8±7.2小时内排斥ACI心脏同种异体移植，而未致敏对照的排斥时间为6.5±0.5天（p＜0.001）。在ACI心脏移植后立即向未致敏的Lewis大鼠注射1ml高滴度CAA导致ACI心脏在2.1±0.8小时内发生超急性排斥，而注射1ml CAA后再注射2ml豚鼠补体（GPC）导致排斥反应更快（平均存活时间（MST）为23.8±4.7分钟）。单独注射2ml GPC或与1ml未致敏Lewis血清联合注射对移植存活没有影响。相对于移植在第 -3、-2、-1和0天多次预先注射1ml CAA导致同种异体移植存活时间显著延长（MST为10.3±0.3天；P＜0.01）。在第2组（中等反应性受体）中，Lewis大鼠预先对WF品系致敏，细胞毒性滴度为1:16至1:256，与未致敏的对照受体相比，受体在23.8±5.8小时内排斥WF心脏，未致敏对照受体的排斥时间为6.8±0.8天（P＜0.001）。注射1ml Lewis抗WF CAA导致移植存活时间延长至9.7±3.5天，而注射1ml CAA后再注射2ml GPC在104±61.7分钟内导致超急性排斥。在第 -3、-2、-1和0天预先注射CAA导致移植增强，MST为16.3±1.3天（P＜0.001）。在第3组（低反应性受体）中，预先对Lewis致敏的ACI产生的细胞毒性滴度为1:2至1:32，与未致敏的受体相比，在5.3±0.4天内排斥Lewis心脏，未致敏受体的排斥时间为10.6±1.0天。（摘要截于400字）
