Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes
Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes
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DOI：
10.1038/34419
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发表时间：
1998-01-08
期刊：
影响因子：
64.8
通讯作者：
Hafler, DA
中科院分区：
文献类型：
--
作者：
Wilson, SB;Kent, SC;Hafler, DA
1 型糖尿病（胰岛素依赖性糖尿病，IDDM）是一种由主要组织相容性复合体 (MHC) 控制的疾病，该复合体是由 T 细胞介导的胰腺 β 细胞破坏所致 (1)。同卵双胞胎中的不完全一致性以及未患糖尿病的个体中存在自身反应性 T 细胞和自身抗体表明，免疫系统中必须出现其他异常才会导致疾病 (2,3)。因此，我们调查了一系列有风险的非进展者和 1 型糖尿病患者（包括五组疾病不一致的同卵双胞胎/三胞胎组）。与非糖尿病兄弟姐妹相比，糖尿病兄弟姐妹的 CD4(-)CD8(-)V α 24J α Q(+) T 细胞频率较低。从糖尿病双胞胎/三胞胎中分离出的所有 56 个 V α 24J α Q(+) 克隆在刺激后仅分泌干扰素 (IFN)-γ；相比之下，来自有风险的非进展者和正常人的 79 个克隆中有 76 个同时分泌白细胞介素 (IL)-4 和 IFN-γ。一半的高危非进展者血清 IL-4 和 IFN-γ 水平较高。这些结果支持 IDDM 模型，其中 Th1 细胞介导的组织损伤最初由产生两种细胞因子的 V α 24J α Q(+) T 细胞调节；他们分泌 IL-4 能力的丧失与 IDDM 相关。
Type 1 diabetes (insulin-dependent diabetes-mellitus, IDDM) is a disease controlled by the major histocompatibility complex (MHC) which results from T-cell-mediated destruction of pancreatic beta-cells(1). The incomplete concordance in identical twins and the presence of autoreactive T cells and autoantibodies in individuals who do not develop diabetes suggest that other abnormalities must occur in the immune system for disease to result(2,3). We therefore investigated a series of at-risk non-progressors and type 1 diabetic patients (including five identical twin/tripiet sets discordant for disease). The diabetic siblings had lower frequencies of CD4(-)CD8(-)V alpha 24J alpha Q(+) T cells compared with their non-diabetic sibling, All 56 V alpha 24J alpha Q(+) clones isolated from the diabetic twins/triplets secreted only interferon (IFN)-gamma upon stimulation; in contrast, 76 of 79 clones from the at-risk non-progressors and normals secreted both interleukin (IL)-4 and IFN-gamma. Half of the at-risk non-progressors had high serum levels of IL-4 and IFN-gamma. These results support a model for IDDM in which Th1-cell-mediated tissue damage is initially regulated by V alpha 24J alpha Q(+) T cells producing both cytokines; the loss of their capacity to secrete IL-4 is correlated with IDDM.