Regulation of Natural Killer Cell Activity by Transforming Growth Factor-β and Prostaglandin E2

The separate and combined effects of transforming growth factor-β1 (TGF-β1) and prostaglandin E₂ on human natural killer (NK) activity were studied. Peripheral blood lymphocytes (PBL) and large granular lymphocytes (LGL, 70–90% purity) were used as effector cells and K562 as targets. Overnight incubation of the effector cells with TGF-β1 resulted in a significant inhibition of NK activity. TGF-β1 did not influence the expression of CD3, CD 16, CD 18 or CD56 antigens on PBL. Combination of TGF-βl with indomethacin gave the same NK-suppressive effect as TGE-β1 alone, showing that the inhibition of NK acuvity by TGF-β1 is not due to an increase in PGE₂ levels. TGF-β did not influence cAMP level in PBL whereas PGE₂ significantly increased it. On the other hand. TGE-β1 and PGE₂ showed an additive inhibitory effect on NK activity. TGF-β1 did not reduce the binding of PBL and LGL to K562. PGE₂ suppressed the binding and TGF-β1 did not influence this suppression. TGF-β1 also suppressed IL-2-induced activation of NK activity and increase of expression of the granule proteins granzyme A and perforin. PGE₂ did not appear to affect granzyme A and perforin contents. The results indicate that TGF-β1 and PGE₂ suppress NK activity by different mechanisms.