Regulation of cytotoxic T cells by ecto-nicotinamide adenine dinucleotide (NAD) correlates with cell surface GPI-anchored/arginine ADP-ribosyltransferase
| Autor: | J, Wang, E, Nemoto, A Y, Kots, H R, Kaslow, G, Dennert |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
ADP Ribose Transferases
Mice Inbred BALB C Glycosylphosphatidylinositols Phosphoric Diester Hydrolases Phosphatidylinositol Diacylglycerol-Lyase Receptors Antigen T-Cell Cytotoxicity Tests Immunologic Flow Cytometry Lymphocyte Activation NAD Mice Inbred C57BL Mice Phosphoinositide Phospholipase C Animals Calcium Lymphocyte Culture Test Mixed T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 153(9) |
| ISSN: | 0022-1767 |
| Popis: | This report demonstrates that incubation of cytotoxic T cells with NAD causes suppression of their ability to proliferate in response to stimulator cells or to lyse targets. Effects are evident after incubation for 3 h with concentrations of NAD as low as 1 microM and are sustained for many hours after removal of NAD from culture media. Suppression is a result of the failure of CTL to form specific conjugates with targets as well as a lower level of activation in response to TCR-mediated stimulation, although TCR-mediated transmembrane signaling is demonstrable. Metabolites of NAD such as nicotinamide, ADP-ribose, and cyclic-ADP-ribose have no detectable effect, indicating that NAD-glycohydrolase or ADP-ribose cyclase do not mediate suppression. Incubation of intact CTL with [32P]NAD leads to incorporation of 32P into a particulate, subcellular fraction, a reaction that is not inhibitable by ADP-ribose. Hydroxylamine, but not mercuric ion releases [32P]ADP-ribose, whereas phosphodiesterase releases [32P]AMP from the particulate subcellular fraction, suggesting that labeling is a result of enzymatic mono-ADP-ribosylation of arginines. In support of this, treatment of intact CTL with phosphatidylinositol-specific phospholipase C releases an arginine-specific ADP-ribosyltransferase and causes insensitivity to ecto-NAD suppression. These results suggest that a GPI-anchored ADP-ribosyltransferase uses ecto-NAD to ADP-ribosylate proteins that regulate CTL function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|