Charlton B, Bacelj A, Mandel T E
Transplantation Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Diabetes. 1988 Jul;37(7):930-5. doi: 10.2337/diab.37.7.930.
The cellular pathway of beta-cell destruction in type I (insulin-dependent) diabetes is still undefined. L3T4+ T-lymphocytes have a role in both the initiation of insulitis and in recurrent disease in transplanted allogeneic islets in nonobese diabetic (NOD) mice. The roles of macrophages and Lyt2+ T-lymphocytes in beta-cell destruction were studied in cyclophosphamide-induced diabetic NOD mice with silica particles and a rat anti-Lyt2 monoclonal antibody. After administration of cyclophosphamide, 10 of 26 untreated mice and 1 of 21 anti-Lyt2-treated mice became diabetic. Insulitis was significantly reduced in anti-Lyt2-treated mice, and immunocytochemical staining showed a lack of Lyt2+ cells. Only 1 of 19 silica-treated mice became diabetic, compared to 8 of 19 control mice. This study demonstrates that both Lyt2+ T-lymphocytes and macrophages are necessary, but not sufficient, for beta-cell destruction in NOD mice. Therefore, we propose that macrophages present beta-cell antigen to L3T4+ cells, which induce cytotoxic Lyt2+ cells to specifically destroy beta-cells.
I型（胰岛素依赖型）糖尿病中β细胞破坏的细胞途径仍不明确。L3T4 + T淋巴细胞在非肥胖糖尿病（NOD）小鼠移植的同种异体胰岛的胰岛炎起始和复发性疾病中均起作用。在环磷酰胺诱导的糖尿病NOD小鼠中，用二氧化硅颗粒和大鼠抗Lyt2单克隆抗体研究了巨噬细胞和Lyt2 + T淋巴细胞在β细胞破坏中的作用。给予环磷酰胺后，26只未治疗的小鼠中有10只和21只抗Lyt2治疗的小鼠中有1只患糖尿病。抗Lyt2治疗的小鼠胰岛炎明显减轻，免疫细胞化学染色显示缺乏Lyt2 +细胞。19只二氧化硅处理的小鼠中只有1只患糖尿病，而19只对照小鼠中有8只。这项研究表明，Lyt2 + T淋巴细胞和巨噬细胞对于NOD小鼠的β细胞破坏都是必要的，但不是充分的。因此，我们提出巨噬细胞将β细胞抗原呈递给L3T4 +细胞，后者诱导细胞毒性Lyt2 +细胞特异性破坏β细胞。
