T cell growth-promoting activity of interferon-γ. Mitogenic effect of the recombinant cytokine on cells from a human T-chronic lymphocytic leukemia

Interferon-γ (IFN-γ) has previously been described as exerting a growth factor activity for murine and human stimulated normal T lymphocytes, in addition to its established role in regulating the cytotoxic activity of T and NK cells. We analyzed the effect of human recombinant IFN-γ on the proliferation of leukemic lymphocytes isolated from the peripheral blood of a patient affected by a T-cell chronic lymphocytic leukemia (T-CLL). Incubation with IFN-γ induced the proliferation of unstimulated leukemic cells. Cell proliferation was maximal after 6 days of culture with the cytokine; the half-maximal effect of IFN-γ was observed at a concentration of approximately 800 U/ml. We also measured the production of IFN-γ by leukemic cells. Cells incubated in control medium released small quantities of IFN-γ activity, while the addition of low doses of the exogenous cytokine to the cell cultures induced high levels of IFN-γ mRNA and protein production. Furthermore, anti-HLA class I monoclonal antibodies, that exert a mitogenic effect on these neoplastic lymphocytes, also induced the IFN-γ gene expression in the same cells. These results indicate that IFN-γ may stimulate the proliferation of human neoplastic T cells and suggest that this cytokine might have a role in the expansion of T-leukemic cell clones in vivo.