Immunogenization of a murine T-cell lymphoma via transfection with interferon-gamma

Tumor cell variants were derived from the BW5147 T-cell lymphoma that differ in major histocompatibility complex (MHC) class I antigen expression, tumorigenicity and metastatic potential. In general, increased H-2K(k) expression was found to be correlated with a reduced tumorigenicity and spontaneous metastasis. CD8+ T cells were identified in the immune recognition of such variants, implicating a role for H-2K(k) in the presentation of tumor-associated antigens. In the present study, H-2K(k+) BW variants were transfected with a gene encoding interferon-γ (IFN-γ), a potent inducer of MHC class I expression. The resulting transfectants exhibited an increased expression of H-2K(k) and concomitantly an inability to generate visible tumors and a reduced metastatic capacity. Furthermore, immunization with the IFN-γ transfectants resulted in an increased generation of cytotoxic T lymphocytes (CTLs) that lysed both the transfectants and the parental tumor cells. Based on these results, vaccinations with the IFN-γ transfectants were performed against the parental tumor cells. The results clearly demonstrated that such vaccinations reduced significantly the tumorigenicity and metastatic capacity of the parental tumor cells. Hence, in this tumor model, IFN-γ gene transfection provides a means to immunogenize H-2K(k+) BW tumor cells.SCOPUS: cp.j