Immunoregulatory role in gamma interferon production by a T cell growth factor-dependent experimental malignant glioma-specific cytotoxic T lymphocyte clone.

The authors have established a murine malignant glioma-specific cytotoxic T lymphocyte clone (G-CTLL 1) by T cell growth factor (TCGF) using 203-glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin). The cloned cells were found to release a large amount of gamma interferon (IFN) in response to glioma-associated antigen-specific stimulation. The authors have investigated whether the IFN produced can contribute to killing the target cells. Adding anti-mouse gamma IFN antibody to the mixed clone-target cell culture inhibited IFN production by the cloned cells but the toxicity of the cells was minimally diminished. Therefore, it is suggested that the endogenous gamma IFN produced by the TCGF-dependent cloned cytotoxic T lymphocyte line does not have direct cytotoxic action on the target cells. Furthermore, IFN production as well as cytotoxicity was blocked by anti-Lyt-2 monoclonal antibody in the absence of complement. This suggests that IFN plays a role in the process of antigen recognition of target cells because the Lyt-2 molecule is involved in an antigen-specific function on the cytotoxic T lymphocyte receptor. The role of TCGF in gamma IFN production was also investigated. The spontaneous production of gamma IFN by the cloned cells paralleled the amounts of exogenous TCGF added to the cultures, but TCGF had no synergistic effect on IFN production in the presence of mitogen or tumor antigen. Accordingly, it is possible that TCGF stimulates the cloned cells to proliferate, causing IFN release.