T lymphopenia in obese diabetic (db/db) mice is non-selective and thymus independent

T lymphopenia in obese diabetic (db/db) mice is non-selective and thymus independent
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DOI:
10.1016/s0024-3205(98)00054-x
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发表时间:
1998-02-27
期刊:
影响因子:
6.1
通讯作者:
Sekihari, H
Sekihari, H
中科院分区:
医学2区
文献类型:
--
作者:
Kimura, M;Tanaka, S;Sekihari, H

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尽管非胰岛素依赖型糖尿病(NIDDM)动物模型C57BL/KsJ db/db小鼠发生T淋巴细胞减少与NIDDM的进展相关,但T淋巴细胞减少尚未得到充分研究。在这项研究中,为了阐明T淋巴细胞减少症在db/db小鼠中发生的方式和原因,我们用流式细胞术纵向检测了脾脏和胸腺的T淋巴细胞亚群,并评估了胸腺切除术和饮食限制对T淋巴细胞减少症发生的影响。8周龄后,当肥胖糖尿病进展时,脾脏和胸腺的T淋巴细胞减少,与瘦(-/X)窝鼠相比,所有T淋巴细胞亚群也同样减少,表明db/db小鼠非选择性T淋巴细胞减少。在T淋巴细胞减少症和NIDDM尚未出现的5周龄行胸腺切除术,对T淋巴细胞减少症的发生无显著影响。此外,配对喂养至30周龄的db/db小鼠体重正常,血糖正常,但仍有明显的高胰岛素血症,但未能纠正T淋巴细胞减少。总之,我们的研究结果表明,在db/db小鼠中,T淋巴细胞减少可能发生非选择性且独立于胸腺功能障碍或肥胖糖尿病。
Although C57BL/KsJ db/db mice, an animal model of non-insulin-dependent diabetes mellitus (NIDDM), develop T lymphopenia in association with the progression of NIDDM, the T lymphopenia has not been fully investigated. In this study, to elucidate how and why T lymphopenia develops in db/db mice, T-lymphocyte subsets in spleen and thymus were longitudinally examined by flow cytometry and the effects of thymectomy and dietary restriction on the development of T lymphopenia were evaluated. After 8 weeks of age, when obese diabetes progresses, T lymphopenia in both spleen and thymus developed and all T-lymphocyte subsets examined were similarly reduced compared to lean (-/X) littermates, indicating non-selective T lymphopenia in db/db mice. Thymectomy performed at 5 wk of age, when neither T lymphopenia nor NIDDM yet presents, had no significant effect on the development of T lymphopenia. Furthermore, pair feeding until 30 weeks of age produced normal body weight and normoglycemia with still marked hyperinsulinemia, but failed to correct T lymphopenia in db/db mice. In conclusion, our results suggest that T lymphopenia may develop non-selectively and independently of either thymic dysfunction or obese diabetes in db/db mice.