ANTITUMOR VACCINATION EFFECT OF DENDRITIC CELLS CAN BE AUGMENTED BY LOCALLY UTILIZING TH1-TYPE CYTOKINES FROM OK432-REACTIVE CD4-CELLS( T)

In order to enhance the antitumor vaccination effect of dendritic cell s (DC) pulsed with class I tumor peptide, we tried to utilize the loca l cytokine help of CD4(+) T cells reactive to a streptococcal preparat ion OK432. DC were prepared from murine bone marrow cells by culture w ith both granulocyte/macrophage-colony-stimulating factor and interleu kin(IL)-4. The peritumoral injections of OK432 induced OK432-reactive CD4(+) T cells in the draining lymph nodes, and their in vitro product ion of interferon gamma was thus significantly enhanced by restimulati on with OK432-pulsed DC. In addition, anti-P815 mastocytoma cytotoxic T lymphocytes were generated from the in vivo OK432-treated P815-drain ing lymph node cells only when the lymph node cells were restimulated in vitro with the DC pulsed with both PIA peptide and OK432. Moreover, the peritumoral injections of OK432 and the subsequent vaccination of the DC, pulsed with both OK432 and PIA peptide, significantly suppres sed the growth of s.c. inoculated P815. Interestingly, a significant l evel of IL-12 was detected in the coculture supernatant of both OK432- pulsed DC and OK432-reactive CD4(+) T cells. Collectively, our results suggest that the antitumor vaccination effect of DC pulsed with class I tumor peptide could thus be effectively augmented by locally utiliz ing the Th1-type cytokines from OK432-reactive CD4(+) T cells.