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.