Helper peptide G89 (HER-2:777-789) and G89-activated cells regulate the survival of effectors induced by the CTL epitope E75 (HER-2, 369-377). Correlation with the IFN-gamma: IL-10 balance

The CTL response to Ag expands after priming and subsequently contracts reducing the number of effectors. CD4+ cells are described as regulators of CTL immunity. To elucidate whether CD4+ cells are involved in survival of effector CTL and the survival signals, we used CTL and Th peptides form the HE...

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Bibliographic Details
Published in:	Anticancer research Vol. 22; no. 3; p. 1481
Main Authors:	Lee, Tom V, Johnston, Dennis A, Thomakos, Nicholas, Honda, Toshie, Efferson, Clay L, Ioannides, Constantin G
Format:	Journal Article
Language:	English
Published:	Greece 01-05-2002
Subjects:	CD40 Antigens - biosynthesis CD40 Antigens - genetics CD40 Antigens - immunology Cell Survival - immunology Cell Survival - physiology Dendritic Cells - immunology Epitopes, T-Lymphocyte - immunology HLA-A2 Antigen - biosynthesis HLA-A2 Antigen - genetics HLA-A2 Antigen - immunology HLA-DR4 Antigen - biosynthesis HLA-DR4 Antigen - genetics HLA-DR4 Antigen - immunology Humans Interferon-gamma - immunology Interferon-gamma - metabolism Interferon-gamma - secretion Interleukin-10 - immunology Interleukin-10 - metabolism Interleukin-10 - secretion Lymphocyte Activation - immunology Peptide Fragments - immunology Receptor, ErbB-2 - immunology T-Lymphocytes, Cytotoxic - cytology T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - immunology Up-Regulation
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Summary:	The CTL response to Ag expands after priming and subsequently contracts reducing the number of effectors. CD4+ cells are described as regulators of CTL immunity. To elucidate whether CD4+ cells are involved in survival of effector CTL and the survival signals, we used CTL and Th peptides form the HER-2 protooncogene recognized in association with HL-A2 and HLA-DR4, respectively. We analyzed the effect of cells stimulated with G89 (777-789) in survival and expression of lytic function of CTL specific for the epitope E75 (369-377). G89 primed cells (G89-PR) and G89 enhanced expansion and Ag-specific cytolyis of CTL at priming with E75, but inhibited survival of E75-specific CTL at restimulation. These effects were not simply a reflection of the increases in IFN-gamma and IL-10, but the ratio IFN-gamma/lL-10 modified by G89 differentially regulated the survival of stimulated cells. This suggests that the use of helper antigens in cancer vaccines should be evaluated in the context of their CTL survival inducing effect.
ISSN:	0250-7005