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Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities.

Publication ,  Journal Article
Bortell, R; Moss, J; McKenna, RC; Rigby, MR; Niedzwiecki, D; Stevens, LA; Patton, WA; Mordes, JP; Greiner, DL; Rossini, AA
Published in: J Immunol
August 15, 2001

The presence of NAD-metabolizing enzymes (e.g., ADP-ribosyltransferase (ART)2) on the surface of immune cells suggests a potential immunomodulatory activity for ecto-NAD or its metabolites at sites of inflammation and cell lysis where extracellular levels of NAD may be high. In vitro, NAD inhibits mitogen-stimulated rat T cell proliferation. To investigate the mechanism of inhibition, the effects of NAD and its metabolites on T cell proliferation were studied using ART2a+ and ART2b+ rat T cells. NAD and ADP-ribose, but not nicotinamide, inhibited proliferation of mitogen-activated T cells independent of ART2 allele-specific expression. Inhibition by P2 purinergic receptor agonists was comparable to that induced by NAD and ADP-ribose; these compounds were more potent than P1 agonists. Analysis of the NAD-metabolizing activity of intact rat T cells demonstrated that ADP-ribose was the predominant metabolite, consistent with the presence of cell surface NAD glycohydrolase (NADase) activities. Treatment of T cells with phosphatidylinositol-specific phospholipase C removed much of the NADase activity, consistent with at least one NADase having a GPI anchor; ART2- T cell subsets contained NADase activity that was not releasable by phosphatidylinositol-specific phospholipase C treatment. Formation of AMP from NAD and ADP-ribose also occurred, a result of cell surface pyrophosphatase activity. Because AMP and its metabolite, adenosine, were less inhibitory to rat T cell proliferation than was NAD or ADP-ribose, pyrophosphatases may serve a regulatory role in modifying the inhibitory effect of ecto-NAD on T cell activation. These data suggest that T cells express multiple NAD and adenine nucleotide-metabolizing activities that together modulate immune function.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

August 15, 2001

Volume

167

Issue

4

Start / End Page

2049 / 2059

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Type C Phospholipases
  • T-Lymphocytes
  • Rats, Inbred WF
  • Rats, Inbred BB
  • Rats
  • Pyrophosphatases
  • Poly(ADP-ribose) Polymerases
  • Phosphorus Radioisotopes
  • Phosphoinositide Phospholipase C
 

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Bortell, R., Moss, J., McKenna, R. C., Rigby, M. R., Niedzwiecki, D., Stevens, L. A., … Rossini, A. A. (2001). Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities. J Immunol, 167(4), 2049–2059. https://doi.org/10.4049/jimmunol.167.4.2049
Bortell, R., J. Moss, R. C. McKenna, M. R. Rigby, D. Niedzwiecki, L. A. Stevens, W. A. Patton, J. P. Mordes, D. L. Greiner, and A. A. Rossini. “Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities.J Immunol 167, no. 4 (August 15, 2001): 2049–59. https://doi.org/10.4049/jimmunol.167.4.2049.
Bortell R, Moss J, McKenna RC, Rigby MR, Niedzwiecki D, Stevens LA, et al. Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities. J Immunol. 2001 Aug 15;167(4):2049–59.
Bortell, R., et al. “Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities.J Immunol, vol. 167, no. 4, Aug. 2001, pp. 2049–59. Pubmed, doi:10.4049/jimmunol.167.4.2049.
Bortell R, Moss J, McKenna RC, Rigby MR, Niedzwiecki D, Stevens LA, Patton WA, Mordes JP, Greiner DL, Rossini AA. Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities. J Immunol. 2001 Aug 15;167(4):2049–2059.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

August 15, 2001

Volume

167

Issue

4

Start / End Page

2049 / 2059

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Type C Phospholipases
  • T-Lymphocytes
  • Rats, Inbred WF
  • Rats, Inbred BB
  • Rats
  • Pyrophosphatases
  • Poly(ADP-ribose) Polymerases
  • Phosphorus Radioisotopes
  • Phosphoinositide Phospholipase C