Differential effects of recombinant interferons alpha, beta, and gamma on induction of human lymphokine (IL-2)-activated killer activity.
The effects of three classes of recombinant interferons (IFN-alpha A, IFN-beta, and IFN-gamma) on maximal induction of lymphokine (IL-2)-activated killer (LAK) activity were studied. Highly purified lymphocytes (greater than 99%) were obtained by counter-flow centrifugal elutriation from peripheral blood of healthy donors. After incubation for 4 days with IL-2 (1 U/ml), purified lymphocytes showed maximal LAK activity against NK cell-resistant target (Daudi) cells, as assessed by 4-hour 51Cr release assay. Addition of exogenous IFN-alpha A or IFN-beta to cultures of lymphocytes plus IL-2 resulted in significant inhibition of LAK activity, but addition of IFN-gamma had no effect on LAK induction by IL-2. IFN-alpha A caused greatest inhibition of LAK activity when added at the start of culture of lymphocytes with IL-2, and was less inhibitory when added 1 day later. Similar inhibition by IFN-alpha A or IFN-beta was observed with nine lines of human tumorigenic cells as targets of LAK activity. IFN-alpha A and IFN-beta also inhibited the proliferative responses of lymphocytes to IL-2 stimulation, and the expression of IL-2 receptors on their surface, whereas IFN-gamma did not. These results suggest that IFN-alpha A and IFN-beta may be important in in situ regulation of LAK cell induction against neoplasms.
D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000145:classification / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000276:immunology
D007370:Interferon Type I; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma