Streptozotocin effects on T lymphocytes and bone marrow cells

The direct immunosuppressant effects of streptozotocin (STZ) have been examined using C3H/HeN mice. Evidence is presented that bone marrow cells and important precursors of T lymphocytes obtained from STZ-diabetic mice are damaged or impaired by the diabetogenic agent. First, insulin treatment (0.2 units, twice daily) for 13 days only partially reversed the fall in number of nucleated cells in the thymus and spleen of STZ-diabetic mice. Second, bone marrow cells from STZ-diabetic mice are unable to reconstitute gamma-irradiated normal syngeneic mice. The survival rate of normal mice given lethal doses of gamma radiation is 100% if they receive bone marrow cells that are injected from untreated syngeneic normal mice. In contrast, irradiated normal mice given donor cells from STZ-treated mice (50-55 days post-STZ) have survival rates of 30% over a 4-week period of observation. These effects are not believed to involve simply a deficiency of insulin because normal syngeneic bone marrow cells completely reconstituted the spleen and thymus of control mice within 29-33 days. STZ-treated mice also have impaired contact sensitivity responses that are not reversed by insulin treatment. These observations suggest that insulin does influence the proliferation of lymphoid cell subpopulations in diabetic animals. However, direct effects of STZ may also occur that irreversibly damage bone marrow cell subpopulations or other important T-cell precursor populations in susceptible strains of mice.