Synergistic effects of interleukin 4 and interleukin 12 on NK cell proliferation.
Our previous studies have demonstrated that interleukin12 (IL-12) (cytotoxic lymphocyte maturation factor/NK cell stimulatory factor) and IL-7 alone have the ability to generate high LAK activity and low proliferative activity in CD56+ NK cells. This study was undertaken to examine the influence of IL-4 on the IL-12-induced activation of CD56+ NK cells. IL-4 did not affect the IL-12-induced generation of LAK activity in CD56+ cells, in contrast to an inhibition of IL-2 and IL-7-induced LAK activity. Most interestingly, the combination of IL-4 and IL-12 resulted in a synergistic proliferative activity (8-fold) in the CD56+ NK cells, and a marked increase in the cell yield at day 5 was detected. Furthermore, the potent effect of IL-4 on IL-12-induced proliferation was restricted to the CD56+ NK cells, as CD56- cell populations were found unresponsive to the combination of IL-4 and IL-12. Furthermore, IL-4 induced a slight increase in the IL-12-stimulated TNF production. IL-12 enhanced the IL-12 receptor (R) expression and IL-4R expression in the CD56+ NK cells. Combined treatment with IL-12 and IL-4 further enhanced the IL-12R expression, most prominently in the CD56+, CD16- NK subpopulation. The increased IL-4R expression induced by IL-12 and the increased IL-12R expression induced by IL-4 may explain the synergistic proliferative activity detected in response to IL-12 and IL-4. IL-4 seems to possess unique stimulatory properties towards resting CD56+ NK cells, when used as a costimulus with IL-12.
Naume
B
B
Institute of Cancer Research, University of Trondheim, Norway.
Gately
M K
MK
Desai
B B
BB
Sundan
A
A
Espevik
T
T
D015703:Antigens, CD / Q000097:blood*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D018664:Interleukin-12; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects
D015703:Antigens, CD; D006133:Growth Substances; D007378:Interleukins; D018664:Interleukin-12; D015847:Interleukin-4