Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection
Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection
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DOI：
10.1385/ijgc:26:1:23
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发表时间：
1999-08-01
期刊：
影响因子：
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通讯作者：
Matsuno, S
中科院分区：
文献类型：
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作者：
Arai, K;Sunamura, M;Matsuno, S
在小鼠胰岛同种异体移植模型中，通过使用针对这些分子的阻断性单克隆抗体（MAbs）来检查阻断细胞间粘附分子-1（ICAM）-1/白细胞功能相关抗原-1（LFA-1）的免疫抑制潜力。从ICR小鼠分离的胰岛移植到链脲佐菌素诱导的糖尿病C57 BL/6小鼠的肾包膜下空间。移植后立即给予抗体，剂量为100 μ g/小鼠/d，持续3或7天。在未治疗的小鼠中，胰岛移植物在16天内被排斥，但单独用抗ICAM-1单克隆抗体（KAT-1）、单独用抗LFA-1单克隆抗体（KBA）或用两种单克隆抗体治疗显著延长了移植物存活。特别是，KAT-1和KBA的组合在7天的过程中产生了显着的延长和诱导无限移植物存活超过100天，在88%的受体。通过逆转录聚合酶链反应（RT-PCR）分析胰岛移植物内细胞因子转录物的表达。在用KAT-1和KBA处理的小鼠中，未检测到Th 1细胞因子（白细胞介素2 [IL-2]和干扰素γ [IFN-γ]）的转录物，但Th 2细胞因子（IL-4和IL-10）的表达增强并持续超过140 d。与此相反，Th 1细胞因子在未处理小鼠的移植物中占主导地位。这些结果表明，抗ICAM-1和/或抗LFA-1单克隆抗体的施用可能通过指示Th 2偏离而降低鼠胰岛同种异体移植物存活率。
Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 mu g/mouse/d for 3 or 7 d. In nontreated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-gamma]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.