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

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.