The induction of in vivo proliferation of long-lived CD44(hi) CD8(+) T cells after the injection of tumor cells expressing IFN-alpha(1) into syngeneic mice

The tumorigenicity of transplantable tumor cells in mice is reduced by tran sduction with cytokine genes, including IFN-alpha and interleukin (IL) 12, Although T cells are considered important in tumor rejection, the mechanism by which genetically modified tumor cells stimulate the immune system has not been examined. In this study, the in vivo proliferation of T-cell subse ts in mice transplanted with cytokine-producing syngeneic tumor cells was a ssessed by administering the DNA precursor bromode-oxyuridine. The injectio n of viable cells producing IFN-alpha or IL-12 caused a marked proliferatio n of CD8(+) T lymphocytes in both the spleen and lymph nodes. Proliferation was most prominent among memory-phenotype CD14(hi) CD8(+) T cells. In cont rast, proliferation of CD8(+) T cells did not occur in mice injected with c ontrol cells or with cells expressing IL-4, granulocyte colony-stimulating factor, or IFN-gamma, Pulse-chase studies in mice injected with IFN-alpha-p roducing cells showed that a proportion of proliferating CD8(+) T cells sur vived for at least 70 days, suggesting that Long-lived memory cells are ind uced using such an approach. In summary, these results, together with previ ous studies on the host immune reactivity triggered by the injection of tum or cells expressing IFN-alpha, represent a strong rationale for considering IFN-alpha as a powerful T-cell adjuvant for the generation of more effecti ve cancer vaccines.