The role of IL-2 and T4+ cells in the generation of human influenza virus-specific CTL activity.
Stimulation of human peripheral blood lymphocytes (PBL) with influenza A virus leads to the generation of virus-specific cytotoxic T lymphocyte (CTL) activity as well as natural killer (NK)-like activity. In this study, we show that exogenous IL-2 augments the in vitro generation of virus-specific CTL activity, only when added some days after the initiation of the culture. Apparently, the endogenously produced IL-2 can be a limiting factor in the in vitro generation of CTL activity. The increase of influenza virus-specific CTL activity after addition of exogenous IL-2 does not affect the restriction pattern of the CTL response. So, the preferential use of certain HLA antigens as restriction elements is not due to a limiting amount of endogenously produced IL-2. Depletion of T4+ cells completely abrogates the generation of virus-specific CTL activity. Addition of exogenous IL-2 to T4+-cell-depleted cultures fully restores the generation of HLA-restricted virus-specific CTL activity. We conclude that in the in vitro generation of virus-specific CTL activity in bulk cultures of human PBL the sole function of T4+ cells in human virus-specific CTL generation is the production of IL-2, no cognitive cell interaction of T8+ CTL precursors with T4+ cells is required, and in bulk cultures T8+ cells themselves are not able to produce sufficient amounts of IL-2 to ascertain the maturation of virus-specific CTL precursors into cytolytic T cells. Finally, we show that exogenous IL-2 also has a stimulatory effect on the NK-like or lymphokine-activated killer activity, which is always concomitantly induced in virus-specific CTL generation cultures, but has no influence on the levels of IFN produced in such cultures.
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D006680:HLA Antigens; D007376:Interleukin-2