alpha/beta-T cell receptor (TCR)+CD4-CD8- (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10.
alpha/beta-T cell receptor (TCR)+CD4-CD8- (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10.
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DOI：
10.1084/jem.187.7.1047
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发表时间：
1998-04-06
期刊：
影响因子：
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通讯作者：
Baxter AG
中科院分区：
文献类型：
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作者：
Hammond KJ;Poulton LD;Palmisano LJ;Silveira PA;Godfrey DI;Baxter AG
我们之前已经证明，非肥胖糖尿病（NOD）小鼠选择性缺乏α/β-T细胞受体（TCR）+CD 4 − CD 8 − NKT细胞，这一缺陷可能导致其对胰岛素依赖型糖尿病（IDDM）自发发展的易感性。通过向年轻雌性NOD小鼠输注胸腺细胞亚群来研究NKT细胞在NOD小鼠中对IDDM的保护作用。单次静脉注射106个来自雌性（BALB/c × NOD）F1供体的CD 4 −/lowCD 8 −或CD 4 − CD 8 −胸腺细胞可保护完整NOD小鼠免于临床IDDM的自发发作。胰岛炎仍然存在于一些受体小鼠，虽然细胞浸润主要是导管周围和胰岛周围，而不是胰岛内模式的特点，胰岛炎在未经处理的NOD小鼠。保护作用与诱导“同种异体耐受”或系统性自身免疫无关。将NOD供体的脾细胞注射到受照射的成年NOD受体后，加速的IDDM发生。当CD 4 − CD 8 −胸腺细胞的α/β-TCR+和α/β-TCR−亚群与致糖尿病脾细胞一起转移，并比较它们在受辐射的成年受者中预防IDDM发展的能力时，只有α/β-TCR+群体具有保护性，证实NKT细胞负责这种活性。在诱导的IDDM模型中的保护作用被体内抗IL-4和抗IL-10单克隆抗体中和，表明这些细胞因子中的至少一种在NKT细胞介导的保护中起作用。这些结果对人类胰岛素依赖型糖尿病的发病机制和潜在预防具有重要意义。
We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in α/β-T cell receptor (TCR)+CD4−CD8− NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM in NOD mice was studied by the infusion of thymocyte subsets into young female NOD mice. A single intravenous injection of 106 CD4−/lowCD8− or CD4−CD8− thymocytes from female (BALB/c × NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. Insulitis was still present in some recipient mice, although the cell infiltrates were principally periductal and periislet, rather than the intraislet pattern characteristic of insulitis in unmanipulated NOD mice. Protection was not associated with the induction of “allogenic tolerance” or systemic autoimmunity. Accelerated IDDM occurs after injection of splenocytes from NOD donors into irradiated adult NOD recipients. When α/β-TCR+ and α/β-TCR− subsets of CD4−CD8− thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the α/β-TCR+ population was protective, confirming that NKT cells were responsible for this activity. The protective effect in the induced model of IDDM was neutralized by anti–IL-4 and anti–IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. These results have significant implications for the pathogenesis and potential prevention of IDDM in humans.