Cytotoxic activity of T lymphocytes is induced upon stimulation with IL-3 plus GM-CSF in animal leukemia model

Chemotherapy for leukemia has severe toxicity and bone marrow transplantation is both financially and logistically demanding. Therefore, immunotherapy is a feasible and promising approach to treat leukemia. For immunotherapy, cytotoxic T lymphocytes (CTL) against leukemic cells were induced. In BALB/c mice, leukemia was induced by N-ethyl-N'-nitrosourea (ENU). The mice were treated with recombinant IL-3 and GM-CSF - both 5μg/kg/day for four days to induce functional CTL. The IL-3+GM-CSF treatment increased total leukocyte counts, accompanied by significant increase in CTL activity, in the leukemic mice. The IL-3+GM-CSF treatment also enhanced the expression of both p40 and p35 isoforms of IL-12. Perforin and granzyme B expressions were increased in the treated group supporting the T lymphocyte-mediated cytotoxic killing of the target cells. The protein tyrosine kinase (PTK) activity was increased in leukemia but decreased after the treatment with IL-3 and GM-CSF. Interferon gamma (IFN-γ) production was decreased in leukemic condition but increased after the treatment with these colony stimulating factors. These data indicate the anti-leukemic potential of the IL-3 and GM-CSF combination therapy.