title: Dose-dependent and schedule-dependent effects of interleukin-12 on antigen-specific CD8 responses.
abstract: Interleukin-12 (IL-12) has been shown to play a central role in the innate and acquired immune responses. Its activities include enhancement of natural killer (NK) and cytotoxic T lymphocyte (CTL) activity and promotion of CD4 Th1 cell development. It has also been shown to provide potent activity as a vaccine adjuvant in generating antibody and T cell responses. We have investigated the efficacy of IL-12 protein in promoting CD8 T cell responses when it is used as an adjuvant for immunization. Studies using, as antigen, cDNA from an autologous antigen (P1A) as well as studies of responses to vaccinia virus-delivered self (gp100) and non-self (beta-galactosidase) antigens show that the dose and schedule of IL-12 administration can significantly affect adjuvant activity, leading to enhancement or suppression of antigen-specific responses.
authors.affiliation: Genetics Institute, Andover, MA 01810, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: W W
authors.initials: WW
authors.lastname: Overwijk
authors.forename: M
authors.initials: M
authors.lastname: O'Toole
authors.forename: H
authors.initials: H
authors.lastname: Swiniarski
authors.forename: N P
authors.initials: NP
authors.lastname: Restifo
authors.forename: A J
authors.initials: AJ
authors.lastname: Dorner
authors.forename: S F
authors.initials: SF
authors.lastname: Wolf
authors.forename: K
authors.initials: K
authors.lastname: Sturmhoefel
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007114:Immunization; D018664:Interleukin-12 / Q000008:administration & dosage*; D012515:Mast-Cell Sarcoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; C076546:tumor rejection antigen P815A, mouse; D018664:Interleukin-12