title: Antigen-specific CD4+ T-cell help is required to activate a memory CD8+ T cell to a fully functional tumor killer cell.
abstract: Although the importance of CD4+ T-cell help for generation of an effective CD8+ effector cytotoxic T cell (CTL) response is well established, the role of T-cell help in the activation of memory T cells to become fully functional tumor killer cells is undefined. Using synthetic peptide immunizations corresponding to the major CTLs and T-helper epitopes of ovalbumin, adoptive transfers of ovalbumin-specific memory CTLs (mCTLs), and ovalbumin as the tumor-specific antigen in a mouse tumor model, we have determined that T help is essential for the activation of mCTLs to kill tumors. Our data show that T-helper cells specific for the tumor-associated antigen are required for the reactivation of mCTLs by antigen presented indirectly from tumor. In contrast, effector CTLs do not need T help to kill tumors. These results have implications for induction of tumor immunotherapy by immunization.
authors.affiliation: Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
authors.forename: Feng Guang
authors.initials: FG
authors.lastname: Gao
authors.forename: Vithagna
authors.initials: V
authors.lastname: Khammanivong
authors.forename: Wen Jun
authors.initials: WJ
authors.lastname: Liu
authors.forename: Graham R
authors.initials: GR
authors.lastname: Leggatt
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D004527:Egg Proteins / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin