Vaccination with activated B cells pulsed with tumor-lysates can induce tumor-specific CD4+ T cells in vivo.
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 derivative from mycobacterium tuberculosis (PPD), showed a proliferative response in the presence of both syngeneic activated B cells and PPD in a major histocompatibility complex class II-restricted manner. For B cells to function as efficient antigen presenting cells, they need to be activated. Both irradiation and several inhibitors for antigen-processing were observed to block the antigen-presenting ability of activated B cells. Based in these findings, the possibility of anti-tumor vaccination with activated B cells was thus investigated. The spleen cells from mice, which were immunized with activated B cells pulsed with B16 melanoma-lysates, produced a higher level of interferon (IFN)-gamma than those from mice, which were immunized with either non-pulsed activated B cells or the tumor-lysates alone, after in vitro restimulation. This IFN-gamma production was also dependent on the CD4+ T cells. Moreover, the splenic CD4+ T cells in such mice were suggested to increase their ability to generate B16 melanoma-specific cytotoxic T lymphocytes after in vitro restimulation. Even more importantly, immunization with B16 melanoma lysate-pulsed activated B cells elicited a protective immunity against B16 melanoma at rechallenge. Collectively, these results indicate that an anti-tumor effect could be induced by immunization with activated B cells, pulsed with the tumor-lysates, by eliciting tumor-specific IFN-gamma producing CD4+ T cells in vivo.
Ito
O
O
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Harada
M
M
Takenoyama
M
M
Tamada
K
K
Li
T
T
Abe
K
K
Fujie
H
H
Nomoto
K
K
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination
D014373:Tuberculin; D007371:Interferon-gamma