Early Th1 Response in Unprimed Nonobese Diabetic Mice to the Tyrosine Phosphatase-Like Insulinoma-Associated Protein 2, an Autoantigen in Type 1 Diabetes
Early Th1 Response in Unprimed Nonobese Diabetic Mice to the Tyrosine Phosphatase-Like Insulinoma-Associated Protein 2, an Autoantigen in Type 1 Diabetes
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未引发的非肥胖糖尿病小鼠对酪氨酸磷酸酶样胰岛素瘤相关蛋白 2（1 型糖尿病的一种自身抗原）的早期 Th1 反应
作者：
S. Trembleau;G. Penna;S. Gregori;G. Magistrelli;A. Isacchi;L. Adorini
The insulinoma-associated protein 2 (IA-2) is a phosphatase-like autoantigen inducing T and B cell responses associated with human insulin-dependent diabetes mellitus (IDDM). We now report that T cell responses to IA-2 can also be detected in the nonobese diabetic (NOD) mouse, a model of human IDDM. Cytokine secretion in response to purified mouse rIA-2, characterized by high IFN-γ and relatively low IL-10 and IL-6 secretion, was elicited in spleen cells from unprimed NOD mice. Conversely, no response to IA-2 was induced in spleen cells from BALB/c, C57BL/6, or Biozzi AB/H mice that express, like NOD, the I-Ag7 class II molecule, but are not susceptible to spontaneous IDDM. The IA-2-induced IFN-γ response in NOD spleen cells could already be detected at 3 wk and peaked at 8 wk of age, whereas the IL-10 secretion was maximal at 4 wk of age and then waned. IA-2-dependent IFN-γ secretion was induced in CD4+ cells from spleen as well as pancreatic and mesenteric lymph nodes. It required Ag presentation by I-Ag7 molecules and engagement of the CD4 coreceptor. Interestingly, cytokines were produced in the absence of cell proliferation and IL-2 secretion. The biological relevance of the response to IA-2 is indicated by the enhanced IDDM following a single injection of the recombinant protein emulsified in IFA into 18-day-old NOD mice. In addition, IFN-γ production in response to IA-2 and IDDM acceleration could be induced by IL-12 administration to 12-day-old NOD mice. These results identify IA-2 as an early T cell-inducing autoantigen in the NOD mouse and indicate a role for the IA-2-induced Th1 cell response in IDDM pathogenesis.
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DOI：
10.1073/pnas.93.2.956
发表时间：
1996-01-23
影响因子：
11.1
作者：
Daniel, D;Wegmann, DR
通讯作者：
Wegmann, DR
影响因子：
4.4
作者：
X. Zheng;A. Steele;Wayne W. Hancock;A. Stevens;Peter W. Nickerson;Prabir Roy-Chaudhury;Y. Tian;Terry B. Strom
通讯作者：
X. Zheng;A. Steele;Wayne W. Hancock;A. Stevens;Peter W. Nickerson;Prabir Roy-Chaudhury;Y. Tian;Terry B. Strom
非肥胖糖尿病小鼠 T 抑制细胞功能激活缺陷。
DOI：
--
发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Serreze,DV;Leiter,EH
通讯作者：
Leiter,EH
影响因子：
15.9
作者：
Zekzer, D;Wong, FS;Sherwin, RS
通讯作者：
Sherwin, RS
NOD 小鼠对噬菌蛋白的细胞免疫反应：克隆 T 细胞导致胰岛移植物遭到破坏。
影响因子：
7.7
作者：
Kelemen,K;Crawford,ML;Gill,RG;Hutton,JC;Wegmann,D
通讯作者：
Wegmann,D