IL-2-lndependent Activity of IL-7 in the Generation of Secondary Antigen-Specific Cytototoxic T Cell Responses in Vitro

Purified CD8⁺ splenocytes from influenza virus strain A/WSN/33 (H₁N₁)-immune BALB/c (H-2^d) mice responded to a synthetic peptide, synthetic influenza nucleoprotein peptide 147-158 R^-, with a sequence (147-158 R156^-) derived from influenza A virus nucleoprotein with high affinity for K^d class I MHC molecules, with the generation of effector cytotoxic T (Tc) cells specific for influenza A virus-infected target cells in vitro. The process of the conversion of synthetic influenza nucleoprotein peptide 147-158 R^- -K^d-responding memory Tc into effector Tc cells requires Ag in the form of peptide associated with K^d class I MHC molecules and the presence of endogenously produced IL-2 by CD8⁺ T cells. Under blockade of utilization of endogenous IL-2 by mAb to IL-2 or IL-2R, no effector Tc cells were generated, but the addition of IL-7 restored the process of the conversion of CD8⁺ memory into effector Tc cells and significantly enhanced the specific cytolytic activity of Tc cells above those of controls. IL-7-reactive cells were found in both IL-2R^high- and IL-2R^low-expressing responder CD8⁺ T cells. We conclude that the requirement for endogenous IL-2 in Ag-induced conversion of CD8⁺ memory Tc cells into effector Tc cells can be replaced by exogenous IL-7. This demonstrates that IL-7 is a potent regulatory cytokine with similar activity to IL-2 and may act independently of IL-2 in the Ag-specific activation of memory CD8⁺ Tc cells.