Regulation of immune function by adp-ribosylation: Il-2-mediated induction in human nk cells of an nad:arginine adpribosyltransferase

I. J. Okasaki, J. S. Miller, J. Moss

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Natural killer (NK) cells are a distinct lineage of lymphocytes that are capable of major histocompatability complex-independent cell killing, a function important in immune surveillance. It has been shown (Wang et al., (1994) J Immunol 1, 4048) that incubation of cytotoxic T lymphocytes (CTL), which complement NK cell immune surveillance, with NAD led to inhibition of proliferation and cytotoxicity, an effect believed to result from ADP-ribosylation of membrane proteins on arginine residues by a glycosylphosphatidylinositol (GPI)-anchored ADPribosyltransferase. In this study, we determined whether human NK cells, similar to CTL, also possess cell surface ADP-ribosyltransferase activity. NK celts expanded for 18 days in the presence of IL-, but not resting cells (without IL-2), demonstrated membrane-bound NAD:arginine ADP-ribosyltransferase and NAD glycohydrolase activities with NADase activity being -100-fold that of transferase activity. In contrast to results with CTL, the enzyme activities in NK cells were not released from the membrane by treatment of cells with phosphatidylinositolspecific phospholipase C (PIPLC), suggesting that they were not GPI-anchored proteins. Since some ADP-ribosyltransferases are structurally similar, we hypothesized that the NK cell transferase might be similar to the lymphocyte GPI-anchored ADP-ribosyltransferase that we cloned previously. Using the GPl-linked transferase cDNA as a probe, a second transferase was cloned from T cell lymphoma (Yac-1) cells and expressed in an NMU cell line. Similar to the activities found on the surface of the NK cells, the expressed protein was a PIPLC-resistant exoenzyme possessing NADase activity in 50-fold excess of NAD:arginine ADP-ribosyltransferase activity. These studies are compatible with the hypothesis that ADP-ribosylation is involved in regulating the function of NK cells.

Original languageEnglish (US)
Pages (from-to)241a
JournalJournal of Investigative Medicine
Issue number3
StatePublished - Jan 1 1996


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