IL-2-independent activity of IL-7 in the generation of secondary antigen-specific cytotoxic T cell responses in vitro.
Purified CD8+ splenocytes from influenza virus strain A/WSN/33 (H1N1)-immune BALB/c (H-2d) 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 Kd 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 147-158R- -Kd-responding memory Tc into effector Tc cells requires Ag in the form of peptide associated with Kd 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-2Rhigh- and IL-2Rlow-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.
Kos
F J
FJ
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Müllbacher
A
A
D000818:Animals; D000941:Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D000941:Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D015851:Interleukin-7; D015375:Receptors, Interleukin-2