Induction of tumor-specific T cell response by cognating tumor cells with foreign antigen-primed Th cells

Abstract

Sufficient CD4+ T cell help is very important in generating specific cytotoxic T cell responses. The inadequate activation of tumor-specific Th cells leads to failure of antitumor immunity. In general, each individual consists of some primed Th cells responding to certain antigens. If these tumor non-specific pre-primed Th cells can provide sufficient help, the generation of tumor-specific T cells may be enhanced. In the present study, we tested this hypothesis by cognating and reactivating pre-primed ovalbumin (OVA)-specific Th cells with OVA-pulsed tumor cells which could simultaneously present both OVA and tumor-associated antigen on the same cell. We clearly demonstrated that immunization of OVA-sensitized mice with OVA-pulsed P388 cells, but not unpulsed P388 cells, led to the induction of P388-specific cytotoxicity and tumor resistance. Both CD4+ and CD8+ tumor-specific cytotoxic T cells were detected in vitro, but only CD8+ T cells played the major effector role in preventing the growth of challenged tumor in vivo. Taken together, our study demonstrated that the immunogenicity of tumor cells can be enhanced effectively by cognating pre-primed foreign antigen-specific Th cells with tumor cells. These findings have potential implications in developing methods to control tumor growth.