Krieger N R, Most D, Bromberg J S, Holm B, Huie P, Sibley R K, Dafoe D C, Alfrey E J
Department of Surgery, Stanford University, California 94305, USA.
Transplantation. 1996 Nov 15;62(9):1285-92. doi: 10.1097/00007890-199611150-00019.
Anti-CD2 monoclonal antibody OX34 has been shown to suppress immunity in rodents in vitro and in vivo. To evaluate the effects of OX34 on vascularized allografts, Lewis (RT1(1)) hearts were transplanted heterotopically into Wistar Furth (RT1(u)) rats. A single 5 mg/kg intraperitoneal dose of OX34 administered at transplantation induced indefinite graft survival (mean survival time >140.3+/-12.3 vs. 12.7+/-0.7 control, P=0.001). The mixed lymphocyte response was partially inhibited at 60 days after transplant, returning to normal at 100 days. Donor-specific tolerance was confirmed by acceptance of second donor (>100 days, n=2) and rejection of third-party (mean survival time: 7.5+/-0.5 days, n=2) hearts. Immunohistochemical staining of allograft tissue from tolerant animals demonstrated abundant CD2+, CD4+, and CD8+ graft-infiltrating cells. To elucidate further the nature of these cells, we compared the expression of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma mRNA in allografted tissue from tolerant, acutely rejecting (AR), isografted, and naive animals using nonisotopic in situ hybridization. A significant increase in IL-2, IL-4, IL-10, and IFN-gamma mRNA was observed in graft-infiltrating cells of both tolerant and AR animals. IL-10 mRNA expression 4 days after transplant was significantly elevated in the OX34-treated compared to AR recipients. These data demonstrate that a single dose of OX34 at engraftment induces tolerance to vascularized allografts. Expression of both T helper 1 and T helper 2 cytokine mRNA profiles (IL-2/IFN-gamma and IL-4/ IL-10, respectively) are up-regulated locally in graft-infiltrating cells of AR and tolerant animal allografts.
抗CD2单克隆抗体OX34已被证明在体外和体内均可抑制啮齿动物的免疫反应。为了评估OX34对血管化同种异体移植物的影响，将Lewis（RT1(1)）心脏异位移植到Wistar Furth（RT1(u)）大鼠体内。在移植时腹腔注射单次5 mg/kg剂量的OX34可使移植物无限期存活（平均存活时间>140.3±12.3天，而对照组为12.7±0.7天，P = 0.001）。移植后60天混合淋巴细胞反应受到部分抑制，100天时恢复正常。通过接受第二个供体心脏（>100天，n = 2）和排斥第三方心脏（平均存活时间：7.5±0.5天，n = 2）证实了供体特异性耐受。对耐受动物的同种异体移植组织进行免疫组织化学染色显示，有大量CD2+、CD4+和CD8+移植物浸润细胞。为了进一步阐明这些细胞的性质，我们使用非同位素原位杂交比较了耐受、急性排斥（AR）、同基因移植和未处理动物的同种异体移植组织中白细胞介素（IL）-2、IL-4、IL-10和干扰素（IFN）-γ mRNA的表达。在耐受和AR动物的移植物浸润细胞中均观察到IL-2、IL-4、IL-10和IFN-γ mRNA显著增加。与AR受体相比，OX34处理组移植后4天IL-10 mRNA表达显著升高。这些数据表明，植入时单次剂量的OX34可诱导对血管化同种异体移植物的耐受。在AR和耐受动物同种异体移植物的移植物浸润细胞中，T辅助细胞1和T辅助细胞2细胞因子mRNA谱（分别为IL-2/IFN-γ和IL-4/IL-10）的表达均在局部上调。
