Innate and adaptive immunity to tumors: IL-12 is required for optimal responses.
We have investigated the importance of endogenously produced IL-12 in innate and adaptive immunity to tumor transplants. The immunogenic lymphoma RMA and its TAP-deficient variant RMA-S were tested for rejection responses by normal and IL-12-deficient mice. IL-12 was crucial for the immunity induced by one immunization with irradiated RMA cells, as well as for in vivo priming of a CTL response in mixed lymphocyte tumor cultures against this MHC class I-expressing tumor. The defective in vivo response could be overcome by multiple immunizations. In further studies of in vitro CTL responses, we found that IL-12 production from either the antigen-pulsed dendritic cells or from host cells was necessary to obtain strong CTL responses. In the complete absence of IL-12, no or only very weak responses could be detected. NK cell-mediated innate resistance, as assessed in non-immunized mice inoculated with a threshold dose of RMA-S cells, also required IL-12. However, NK cells with reduced activity were present in IL-12-deficient mice and contributed to innate resistance, as demonstrated with lower cell dose challenges. In conclusion, IL-12 is required for optimal adaptive and innate responses against tumors.
Grufman
P
P
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. Per.Grufman@mtc.ki.se
Kärre
K
K
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D017353:Gene Deletion; D006183:H-2 Antigens / Q000276:immunology; D007114:Immunization; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; D010455:Peptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D018664:Interleukin-12