INSULIN-DEPENDENT DIABETES IN THE NOD MOUSE MODEL .2. BETA-CELL DESTRUCTION IN AUTOIMMUNE DIABETES IS A TH2 AND NOT A TH1 MEDIATED EVENT
INSULIN-DEPENDENT DIABETES IN THE NOD MOUSE MODEL .2. BETA-CELL DESTRUCTION IN AUTOIMMUNE DIABETES IS A TH2 AND NOT A TH1 MEDIATED EVENT
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DOI：
10.3109/08916939309043886
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发表时间：
1993-01-01
期刊：
影响因子：
3.5
通讯作者：
PECK, AB
中科院分区：
文献类型：
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作者：
ANDERSON, JT;CORNELIUS, JG;PECK, AB
I型胰岛素依赖型糖尿病(IDD)在人和动物中都是由胰腺β细胞的特定自身免疫破坏引起的，涉及体液免疫和细胞免疫机制。病理性组织学病变称为胰腺炎，是胰岛细胞的炎性和免疫细胞浸润性病变。虽然最近的组织学和流式细胞术分析已经确定了浸润物的细胞成分，但细胞群的存在可能不能反映对β细胞破坏重要的功能反应。在目前的研究中，我们通过测量增加的细胞因子mRNA的使用来研究胰岛浸润性单个核细胞群体可能的功能反应性。结果表明：1)NOD雌性和雄性NOD小鼠胰岛浸润性细胞因子表达谱相似，但IL-2受体和IL-1α表达水平存在显著差异；2)CD4+T淋巴细胞表达IL-4，可能是IL-5，偶尔表达IL-10，但未检测到IL-2mRNA；这些发现，加上我们早期对胰岛浸润性细胞的流式细胞术分析，使得构建自身免疫性糖尿病自然病史的详细模型成为可能。有趣的是，这个模型基于T(H2)而不是T(H1)介导的方案，对目前被认为构成IDD自身免疫反应基础的更流行的概念提出了质疑。
Type I, insulin-dependent diabetes (IDD) in both man and animals results from a specific autoimmune destruction of the pancreatic beta cells involving both humoral and cellular immune mechanisms. The pathognomonic histologic lesion, termed insulitis, is an inflammatory and immune cell infiltrate of the pancreatic islet cells. While recent histological and flow cytometric analyses have identified the cell composition of the infiltrate, the presence of a cell population may not reflect the functional reactivities important for beta cell destruction. In the present study, we have investigated the possible functional reactivities of islet-infiltrating mononuclear cell populations by measuring increased cytokine mRNA usage. Results indicate that 1) cytokine mRNA profiles exhibited by islet-infiltrating cells of female and male NOD mice were quite similar with the exception of IL-6 expression and the marked differences in the levels of IL-2 receptor and IL-1alpha mRNA, 2) CD4+ T lymphocytes expressed IL-4, presumably IL-5, and occasionally IL-10 mRNA but no detectable IL-2 mRNA, 3) CD8+ T lymphocytes exhibited TNF-beta, perforin and high levels of IFN-gamma, and 4) IL-7 was expressed in the islet at very high levels. These findings, together with our earlier flow cytometric analyses of the islet-infiltrating cells, have permitted construction of a detailed model for the natural history of autoimmune diabetes. Interestingly, this model, based on a T(H2)- and not a T(H1)-mediated scheme, questions the more popular concepts currently thought to form the bases of the autoimmune reactions underlying IDD.