Cyclic AMP upregulates mRNA and surface expression of IL-2R alpha p55(Tac) in normal human NK cell clones.
The effects of cAMP upon cell proliferation, cytotoxic activity, and regulation of IL-2R expression was investigated in normal human, IL-2-dependent natural killer (NK) cell clones. We report here that addition to the cultures of Bt2cAMP, a cell permeant analogue of cAMP, results in inhibition of IL-2-dependent proliferation, as assessed by [3H]Thymidine incorporation, in both NK and T cell clones. In addition, Bt2cAMP was shown to block the cytotoxic activity of NK cell clones at the level of the lytic phase. Contrasting with these inhibitory effects, cAMP induces an upregulation of the membrane expression of the IL-2R alpha chain (p55, Tac) in normal NK cell clones, which correlates with an accumulation of Tac mRNA. This is clearly at variance with T cell clones in which no such effect of cAMP alone is observed. In both cell types however, cAMP appears to synergize with IL-2 to increase IL-2R alpha mRNA expression. In addition, we demonstrate, using a cDNA probe to the IL-2R beta, that expression of this second component of the high affinity IL-2R, does not appear to be co-regulated together with IL-2R alpha in response to cAMP or/and IL-2 in cultured NK cells. Thus the effects of cAMP on human NK cell clones are complex. cAMP is inhibitory of proliferation and cytolytic function, whereas it is stimulatory of IL-2R alpha expression in these cells.
Vitté-Mony
I
I
Institut National de la Santé et de la Recherche Médicale, Unité 333, Institut Gustave Roussy, Villejuif, France.
Goy
A
A
Guizani
L
L
Bertoglio
J H
JH
D015152:Blotting, Northern; D002999:Clone Cells; D000242:Cyclic AMP / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation
D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D000242:Cyclic AMP