VACCINATION WITH ACTIVATED B-CELLS PULSED WITH TUMOR-LYSATES CAN INDUCE TUMOR-SPECIFIC CD4(-CELLS IN-VIVO() T)

Activated B cells, pulsed with tumor-lysates, were examined for their potential to induce tumor-specific CD4(+) T cells in vivo. MH2 cells, which are CD4(+) T cells and can also recognize purified protein deriv ative from mycobacterium tuberculosis (PPD), showed a proliferative re sponse in the presence of both syngeneic activated B cells and PPD in a major histocompatibility complex class II-restricted manner. For B c ells to function as efficient antigen presenting cells, they need to b e activated. Both irradiation and several inhibitors for antigen-proce ssing were observed to block the antigen-presenting ability of activat ed B cells. Based in these findings, the possibility of anti-tumor vac cination with activated B cells was thus investigated. The spleen cell s from mice, which were immunized with activated B cells pulsed with B 16 melanoma-lysates, produced a higher level of interferon (IFN)-gamma than those from mice, which were immunized with either non-pulsed act ivated B cells or the tumor-lysates alone, after in vitro restimulatio n. This IFN-gamma production was also dependent on the CD4(+) T cells. Moreover, the splenic CD4(+) T cells in such mice were suggested to i ncrease their ability to generate B16 melanoma-specific cytotoxic T ly mphocytes after in vitro restimulation. Even more importantly, immuniz ation with B16 melanoma lysate-pulsed activated B cells elicited a pro tective immunity against B16 melanoma at rechallenge. Collectively, th ese results indicate that an anti-tumor effect could be induced by imm unization with activated B cells, pulsed with the tumor-lysates, by el iciting tumor-specific IFN-gamma producing CD4(+) T cells in vivo.