Antigen-specific CD4+ T-cell help is required to activate a memory CD8+ T cell to a fully functional tumor killer cell.
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.
Gao
Feng Guang
FG
Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
Khammanivong
Vithagna
V
Liu
Wen Jun
WJ
Leggatt
Graham R
GR
Frazer
Ian H
IH
Fernando
Germain J P
GJ
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
D000951:Antigens, Neoplasm; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin