Expression of ADP-ribosyltransferase on normal T lymphocytes and effects of nicotinamide adenine dinucleotide on their function.
ADP-ribosyltransferase (ADPRT) is a glycosylphosphatidylinositol-anchored cell surface enzyme on CTL. Expression of this enzyme correlates with suppression of CTL functions in the presence of its substrate beta-nicotinamide adenine dinucleotide (NAD). To investigate the immunoregulatory importance of ADPRT on normal lymphocytes in vivo, NAD was injected into mice and the effects on cell-mediated and humoral immunity were assessed. Induction of both delayed-type hypersensitivity and CTL, but not Ab responses, are shown to be suppressed by NAD. Consistent with this, mature T cells, but not B cells or macrophages, express ADPRT and are able to ADP-ribosylate cell surface proteins. ADP-ribosylated molecules were identified as LFA-1, CD8, CD27, CD43, CD44, and CD45. Concomitant to ADP-ribosylation of these molecules, T cell trafficking to secondary lymphoid organs is suppressed by NAD. To examine whether this is due to effects of NAD on cell activation, Ag-stimulated responses were assayed in vitro. NAD is shown to inhibit induction of cell proliferation, cytotoxicity, and cytokine secretion. It is suggested that ADPRT regulates T cells on the level of transmembrane signaling via ADP-ribosylation of cell surface molecules. This effect is reported to be indirect, as it involves transmission of signals through TCRs, which are not ADP-ribosylated.
Okamoto
S
S
Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Azhipa
O
O
Yu
Y
Y
Russo
E
E
Dennert
G
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D007109:Immunity / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009243:NAD / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D009243:NAD; D011065:Poly(ADP-ribose) Polymerases