Rohane P W, Shimada A, Kim D T, Edwards C T, Charlton B, Shultz L D, Fathman C G
Stanford University School of Medicine, California 94305-5111, USA.
Diabetes. 1995 May;44(5):550-4. doi: 10.2337/diab.44.5.550.
In an effort to study the development of diabetes in NOD mice, our laboratory developed a novel adoptive transfer model using NOD-scid/scid (NOD-scid) mice as recipients of islet-infiltrating lymphocytes from donor prediabetic female NOD mice. We first confirmed previous results that demonstrated that splenocytes of diabetic and prediabetic female NOD mice could transfer diabetes to NOD-scid mice. We demonstrated that the kinetics of disease transfer were dependent on the age of transferred lymphocytes and reiterated the kinetics of diabetes in conventional female NOD mice. We then demonstrated that islet-infiltrating lymphocytes from prediabetic female NOD mice could transfer diabetes. In contrast with the age-dependent transfer of diabetes seen using splenocytes, islet-infiltrating lymphocytes obtained from prediabetic female NOD mice aged > or = 40 days rapidly transferred diabetes to NOD-scid recipients. The time required to transfer insulin-dependent diabetes mellitus (IDDM) using islet-infiltrating lymphocytes from young prediabetic mice (25 +/- 9 days) was not statistically different from the time required to transfer IDDM using splenocytes from overtly diabetic mice (32 +/- 5 days). Cotransfer of splenocyte cells or CD4+, but not CD8+ spleen cells, from 60- to 80-day-old prediabetic female NOD mice together with either splenocytes from diabetic mice or islet-infiltrating lymphocytes from prediabetic NOD mice delayed the rapid transfer of IDDM, suggesting that CD4+ cells mediated immunoregulation. Use of the NOD-scid islet-infiltrating lymphocyte-adoptive transfer model should help elucidate the pathophysiology of the early inflammatory events leading to insulitis and subsequent beta-cell destruction.(ABSTRACT TRUNCATED AT 250 WORDS)
为了研究非肥胖糖尿病（NOD）小鼠糖尿病的发展，我们实验室开发了一种新型的过继转移模型，该模型使用NOD-scid/scid（NOD-scid）小鼠作为受体，接受来自供体糖尿病前期雌性NOD小鼠的胰岛浸润淋巴细胞。我们首先证实了先前的研究结果，即糖尿病和糖尿病前期雌性NOD小鼠的脾细胞能够将糖尿病转移至NOD-scid小鼠。我们证明疾病转移的动力学取决于转移淋巴细胞的年龄，并再次证实了传统雌性NOD小鼠糖尿病的动力学。然后我们证明糖尿病前期雌性NOD小鼠的胰岛浸润淋巴细胞能够转移糖尿病。与使用脾细胞观察到的年龄依赖性糖尿病转移不同，从年龄≥40天的糖尿病前期雌性NOD小鼠获得的胰岛浸润淋巴细胞能迅速将糖尿病转移至NOD-scid受体。使用来自年轻糖尿病前期小鼠（25±9天）的胰岛浸润淋巴细胞转移胰岛素依赖型糖尿病（IDDM）所需的时间与使用明显糖尿病小鼠的脾细胞转移IDDM所需的时间在统计学上无差异（32±5天）。将60至80天龄糖尿病前期雌性NOD小鼠的脾细胞或CD4 +而非CD8 +脾细胞与糖尿病小鼠的脾细胞或糖尿病前期NOD小鼠的胰岛浸润淋巴细胞共同转移，可延迟IDDM的快速转移，这表明CD4 +细胞介导免疫调节。使用NOD-scid胰岛浸润淋巴细胞过继转移模型应有助于阐明导致胰岛炎及随后β细胞破坏的早期炎症事件的病理生理学。（摘要截选至250字）
