In vivo priming effects of interferon-beta ser on NK activity of peripheral blood mononuclear cells in cancer patients.
Natural killer (NK) activity was assayed in fresh peripheral blood mononuclear cells (PBMs) from cancer patients receiving interferon (IFN)-beta ser. Patients received a single intravenous injection of IFN-beta ser (90 x 10(6) IU m-2) on alternate days for 2 weeks, followed by a higher dose (180 x 10(6) IU m-2) on the same schedule. PBM NK lysis of K562 target cells was significantly increased in PBMs sampled 24 h after the initial injection (P < 0.05). At the end of the first 2 weeks of the protocol, NK cytotoxic activity of PBMs had fallen below the original baseline levels; the higher IFN dose subsequently given was without effect. However, significant increases in the proportion of CD16+ cells were seen following each injection. A positive correlation was also seen between the increased lytic activity of CD16+ NK cells and the proportion of CD38+ NK cells, but not the proportion of CD56+ NK cells. In vitro IFN-treatment of these in vivo-treated PBMs resulted in a further increase in NK activity. Pre-exposure in vivo to IFN-beta ser seems to prime the PBMs to respond to in vitro stimulation by IFN-gamma, which otherwise had no effect. Phenotypic analysis of PBMs after in vitro exposure to IFN-beta ser showed that the levels of CD16+, CD38+ and CD56+ cells did not change. All the NK activity responding to IFN-beta ser was found in the CD16+ enriched population of PBM, suggesting that it is unlikely that in vivo redistribution of CD16+ subsets representative of NK cells has occurred in the peripheral blood.
Fujimiya
Y
Y
Section of Immunology, Childrens' Medical Research Center, National Children's Hospital, Tokyo, Japan.
Wagner
R J
RJ
Groveman
S
S
Sielaff
K
K
Kohsaka
T
T
Nakayama
M
M
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood; D019002:CD56 Antigen / Q000097:blood; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000008:administration & dosage; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000097:blood; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D019002:CD56 Antigen; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D000068556:Interferon beta-1a