Diab Randa A H, Hassan Moustapha, Tibell Annika, Holgersson Jan, Kumagai-Braesch Makiko
Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Human Anatomy, School of Medicine, Ahfad University for Women, Omdurman, Sudan.
Xenotransplantation. 2014 Jul-Aug;21(4):353-66. doi: 10.1111/xen.12103. Epub 2014 May 8.
Costimulation blockade can prevent rejection of islet xenografts in naïve but not sensitized recipients. Donor-specific antibodies (DSA) may partly explain this observation. The effect of DSA on rat islet xenograft survival in mice receiving costimulation blockade was investigated.
Naïve C57BL/6 mice with alloxan-induced diabetes were transplanted under the left kidney capsule with 100 Lewis rat islets. Recipients were divided into three groups receiving: (i) isotype control antibodies (Abs); (ii) anti-CD154 and CTLA4Ig; or (iii) anti-CD154, CTLA4Ig, and anti-LFA-1 every second day, day 0-8. At the time of transplantation (Tx), half of the animals in each group received naïve mouse serum and half xenoimmune serum derived from mice previously transplanted with rat islets. Non-fasting blood glucose levels and body weight were followed daily. Cured mice were examined by intraperitoneal glucose tolerance (IPGT) tests at 1 and 4 months after transplantation.
Donor-specific antibodies were detected in immune serum-injected recipients up to at least 96 h post-Tx. Short term (≤96 h), there was no significant difference with regard to graft mass, infiltrating and apoptotic cells between groups of mice receiving naïve and immune sera. A moderate infiltration of polymorphonuclear and mononuclear cells was seen 96 h post-Tx in mice given control Abs, whether or not they received immune or naïve mouse serum. Mice given costimulation blockade had well-maintained endocrine tissue and very little cell infiltration. There was no significant difference in islet xenograft function and survival long term between groups receiving naïve and immune sera in combination with costimulation blockade. About half of the mice receiving costimulation blockade lost graft function within 110 days.
The presence at Tx of DSA does not appear to negatively influence early and late islet xenograft survival in mice receiving costimulation blockade.
共刺激阻断可防止初次接受移植的而非致敏受体排斥胰岛异种移植物。供体特异性抗体（DSA）可能部分解释了这一现象。本研究调查了DSA对接受共刺激阻断的小鼠体内大鼠胰岛异种移植物存活的影响。
用四氧嘧啶诱导糖尿病的初次接受移植的C57BL/6小鼠，于左肾包膜下移植100个Lewis大鼠胰岛。受体分为三组，分别接受：（i）同型对照抗体（Abs）；（ii）抗CD154和CTLA4Ig；或（iii）每隔一天（第0 - 8天）给予抗CD154、CTLA4Ig和抗LFA - 1。在移植时（Tx），每组一半动物接受初次接受移植的小鼠血清，另一半接受先前移植过大鼠胰岛的小鼠的异种免疫血清。每天监测非空腹血糖水平和体重。移植后1个月和4个月通过腹腔葡萄糖耐量（IPGT）试验检查治愈的小鼠。
在移植后至少96小时内，在注射免疫血清的受体中检测到供体特异性抗体。短期（≤96小时）内，接受初次接受移植的小鼠血清和免疫血清的小鼠组之间，在移植物质量、浸润细胞和凋亡细胞方面无显著差异。移植后96小时，给予对照抗体的小鼠，无论接受免疫或初次接受移植的小鼠血清，均可见多形核细胞和单核细胞的中度浸润。给予共刺激阻断的小鼠内分泌组织维持良好，细胞浸润极少。接受初次接受移植的小鼠血清和免疫血清联合共刺激阻断的组之间，胰岛异种移植物功能和长期存活无显著差异。接受共刺激阻断的小鼠中约一半在110天内失去移植物功能。
移植时DSA的存在似乎不会对接受共刺激阻断的小鼠胰岛异种移植物的早期和晚期存活产生负面影响。
