title: Augmented induction of CD8+ cytotoxic T-cell response and antitumour resistance by T helper type 1-inducing peptide.
abstract: The effector CD8(+) T cells recognize major histocompatibility complex (MHC) class I binding altered self-peptides expressed in tumour cells. Although the requirement for CD4(+) T helper type 1 (Th1) cells in regulating CD8(+) T cells has been documented, their target epitopes and functional impact in antitumour responses remain unclear. We examined whether a potent immunogenic peptide of Mycobacterium tuberculosis eliciting Th1 immunity contributes to the generation of CD8(+) T cells and to protective antitumour immune responses to unrelated tumour-specific antigens. Peptide-25, a major Th epitope of Ag85B from M. tuberculosis preferentially induced CD4(+) Th1 cells in C57BL/6 mice and had an augmenting effect on Th1 generation for coimmunized unrelated antigenic peptides. Coimmunization of mice with Peptide-25 and ovalbumin (OVA) or Peptide-25 and B16 melanoma peptide [tyrosinase-related protein-2 (TRP-2)] for MHC class I led to a profound increase in CD8(+) T cells specific for OVA and TRP-2 peptides, respectively. This heightened response depended on Peptide-25-specific CD4(+) T cells and interferon-gamma-producing T cells. In tumour protection assays, immunization with Peptide-25 and OVA resulted in the enhancement of CD8(+) cytotoxic cell generation specific for OVA and the growth inhibition of EL-4 thymoma expressing OVA peptide leading to the tumour rejection. These phenomena were not achieved by immunization with OVA alone. Peptide-25-reactive Th1 cells counteractivated dendritic cells in the presence of Peptide-25 leading them to activate and present OVA peptide to CD8(+) cytotoxic T cells.
authors.affiliation: Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Uehara
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Ariga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokunaga
authors.forename: Ai
authors.initials: A
authors.lastname: Kariyone
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
mesh_terms: D000217:Acyltransferases / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013945:Thymoma / Q000276:immunology / Q000628:therapy*; D013953:Thymus Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000942:Antigens, Bacterial; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D010047:Ovalbumin; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis