Immunization of diabetes-prone or non-diabetes-prone mice with GAD65 does not induce diabetes or islet cell pathology.
Immunization of diabetes-prone or non-diabetes-prone mice with GAD65 does not induce diabetes or islet cell pathology.
复制标题
用 GAD65 免疫有糖尿病倾向或非糖尿病倾向的小鼠不会诱发糖尿病或胰岛细胞病变。
DOI：
10.1006/jaut.1998.0206
复制
发表时间：
1998
影响因子：
12.8
通讯作者：
J. Petersen
中科院分区：
文献类型：
--
作者：
A. Plesner;A. Worsaae;T. Dyrberg;C. Gotfredsen;B. Michelsen;J. Petersen
通过用谷氨酸脱羧酶、GAD 65、牛血清白蛋白或磷酸盐缓冲盐水在不完全弗氏佐剂中免疫雌性BALB/c、C57 B1/6、国家海洋研究所（NMRI）和非肥胖糖尿病（NOD）小鼠一次或两次或不处理来研究谷氨酸脱羧酶自身免疫。用GAD 65免疫的小鼠在体外通过细胞因子分泌评估显示出对GAD 65的脾T细胞反应性。然而，未治疗的NOD小鼠没有。NOD小鼠在一次免疫后显示出强烈的IFN-γ应答，而NMRI小鼠显示出较低的应答。IL-4和IL-10仅在两次免疫后检测到，与C57 B1/6小鼠相比，在BALB/c、NMRI和NOD小鼠中具有更高的水平。在所有用GAD 65免疫的小鼠中检测到高水平的GAD 65抗体，尽管在C57 B1/6小鼠中发现较低水平。胰腺的组织学分析显示，无论给药与否，对照组小鼠的胰岛中均无单核细胞浸润。在NOD小鼠中，在所有组中均检测到胰岛周围炎，但在GAD 65和牛血清白蛋白（BSA）免疫的动物中较少。这些数据表明，NOD小鼠比非糖尿病小鼠品系对GAD 65免疫的反应更强烈。此外，用GAD 65免疫不足以在NOD小鼠中引发糖尿病发作或在非糖尿病易感小鼠中诱导胰岛细胞病理学。
Glutamic acid decarboxylase autoimmunity was investigated by immunizing female BALB/c, C57B1/6, National Marine Research Institute (NMRI) and non-obese diabetic (NOD) mice once or twice with glumatic acid decarboxylase, GAD65, bovine serum albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not treating. Mice immunized with GAD65, showed splinic T-cell reactivity to GAD 65 in vitro assessed by cytokine secretion. However untreated NOD mice did not. NOD mice showed a vigorous IFN-gamma response after one immunization, whereas NMRI mice showed a lower response. IL-4 and IL-10 were only detected after two immunizations with higher levels in BALB/c, NMRI and NOD mice, compared to C57B1/6 mice. High levels of GAD65 antibodies were detected in all mice immunized with GAD65, though lower levels were found in C57B1/6 mice. Histological analysis of pancreata revealed that no control mice, regardless of treatment, had mononuclear cell infiltration in the islets. In NOD mice, peri-insulitis was detected in all groups, but less so in GAD65 and bovine serum albumin (BSA) immunized animals. These data demonstrate that NOD mice respond more vigorously to immunization with GAD65 than non-diabetic mice strains. Furthermore, immunization with GAD65 is not sufficient to provoke onset of diabetes in NOD mice or induce islet cell pathology in non-diabetes prone mice.
DOI：
10.1073/pnas.89.6.2115
发表时间：
1992-03-15
影响因子：
11.1
作者：
BU, DF;ERLANDER, MG;TOBIN, AJ
通讯作者：
TOBIN, AJ