Diabetes prone BB rats are severely deficient in natural killer T cells
Diabetes prone BB rats are severely deficient in natural killer T cells
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DOI：
10.3109/08916939908993854
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发表时间：
1999-01-01
期刊：
影响因子：
3.5
通讯作者：
Mordes, JP
中科院分区：
文献类型：
--
作者：
Iwakoshi, NN;Greiner, DL;Mordes, JP
易患糖尿病 (DP) BE 大鼠会出现自发性自身免疫性高血糖。同源性糖尿病抗性 (DR) BE 大鼠因免疫和环境扰动而患上糖尿病，但不是自发的。两者均用于模拟人类胰岛素依赖性糖尿病 (IDDM)。自然杀伤 (NK) T 细胞的缺陷与人类 IDDM 的表达有关，但对其在大鼠中的表型或功能知之甚少。我们现在报道，大鼠中 NK T 细胞的表型是 α beta TcR(+)CD8(+)CD4(-)，与报道的人类 NK T 细胞表型相当，即 α beta TcR(+)CD4(-)V alpha 24-J alpha Q，以及 CD8(-) 或 CD8 alpha alpha(+)。我们还报告说，DP-而非DR-BE大鼠的脾脏和肝内NKR-P1（+）αβTcR+（NK T）细胞严重缺乏，因为DP-BB大鼠中RT6（+）T细胞缺乏，并且因为表达RT6的细胞的耗竭会在DR-BE大鼠中诱导IDDM，所以我们研究了NK T细胞表达该抗原。我们观察到大多数大鼠 NK T 细胞表达 RT6，此外，注射细胞毒性抗 RT6.1 单克隆抗体耗尽了脾脏和肝内 RT6(+) NK T 细胞、T 细胞和 NK 细胞，但保留了每个群体的 RT6(-) 子集。这些结果表明，NK T 细胞的缺陷可能在 DP- 和 DR-BE 大鼠分别对自发性和诱导性自身免疫性 IDDM 的易感性中发挥作用。
Diabetes prone (DP) BE rats develop spontaneous autoimmune hyperglycemia. Coisogenic diabetes resistant (DR) BE rats develop diabetes in response to immunological and environmental perturbants, but not spontaneously. Both are used to model human insulin-dependent diabetes mellitus (IDDM). Deficiencies in natural killer (NK) T cells have been implicated in the expression of human IDDM, but little is known of their phenotype or function in the rat. We now report that the phenotype of NK T cells in the rat is alpha beta TcR(+)CD8(+)CD4(-), comparable to the NK T cell phenotype reported for humans, which is alpha beta TcR(+)CD4(-)V alpha 24-J alpha Q, and either CD8(-) or CD8 alpha alpha(+). We also report that DP- but not DR-BE rats are severely deficient in splenic and intrahepatic NKR-P1(+) alpha beta TcR+ (NK T) cells, Because RT6(+) T cells are deficient in DP-BB rats, and because depletion of cells expressing RT6 induces IDDM in DR-BE rats, we studied NK T cells for expression of this antigen. We observed that the majority of rat NK T cells express RT6, In addition, injection of cytotoxic anti-RT6.1 monoclonal antibody depleted splenic and intrahepatic RT6(+) NK T cells, T cells, and NK cells, but left intact the RT6(-) subset of each population. These results suggest that deficiencies in NK T cells may play a role in the susceptibility of DP- and DR-BE rats, respectively, to spontaneous and induced autoimmune IDDM.