CD8+ T lymphocytes in viral hyperreactivity and M2 muscarinic receptor dysfunction.

Darryl J. Adamko, Allison Fryer, Bruce S. Bochner, David Jacoby

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

In the airways, inhibitory M2 muscarinic receptors (M2Rs) on parasympathetic nerves limit acetylcholine release. Viral infection causes M2R dysfunction, which increases acetylcholine release and leads to airway hyperreactivity. In these studies we tested the role of CD8+ T cells in parainfluenza virus-induced hyperreactivity and M2R dysfunction in normal guinea pigs and in guinea pigs previously sensitized to ovalbumin. Depleting CD8+ T cells prevented virus-induced M2R dysfunction and hyperreactivity in sensitized animals, but not in nonsensitized animals. Sensitization increased the number of eosinophils in close relation to the airway nerves where, when activated, they release major basic protein, which binds to and blocks the M2Rs. Regardless of sensitization, viral infection decreased the number of visible tissue eosinophils, likely reflecting eosinophil degranulation via cytolysis. Depleting CD8+ T cells prevented this virus-induced eosinophil degranulation. In addition, an antiviral effect of sensitization, which we previously showed to be eosinophil mediated, was again seen. This was prevented by depletion of CD8+ Tcells. Thus, CD8+ T cells play a role in airway hyperreactivity and M2R dysfunction of sensitized virus-infected guinea pigs by mediating eosinophil degranulation near airway nerves. In contrast, CD8+ T cells are not necessary for virus-induced hyperreactivity and M2R dysfunction in nonsensitized guinea pigs.

Original languageEnglish (US)
Pages (from-to)550-556
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume167
Issue number4
StatePublished - Feb 15 2003
Externally publishedYes

Fingerprint

Muscarinic M2 Receptors
Eosinophils
T-Lymphocytes
Viruses
Guinea Pigs
Virus Diseases
Acetylcholine
Paramyxoviridae Infections
Ovalbumin
Antiviral Agents

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

CD8+ T lymphocytes in viral hyperreactivity and M2 muscarinic receptor dysfunction. / Adamko, Darryl J.; Fryer, Allison; Bochner, Bruce S.; Jacoby, David.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 167, No. 4, 15.02.2003, p. 550-556.

Research output: Contribution to journalArticle

@article{37ad9e617fdf4f57a9dac4cb3bd1c40b,
title = "CD8+ T lymphocytes in viral hyperreactivity and M2 muscarinic receptor dysfunction.",
abstract = "In the airways, inhibitory M2 muscarinic receptors (M2Rs) on parasympathetic nerves limit acetylcholine release. Viral infection causes M2R dysfunction, which increases acetylcholine release and leads to airway hyperreactivity. In these studies we tested the role of CD8+ T cells in parainfluenza virus-induced hyperreactivity and M2R dysfunction in normal guinea pigs and in guinea pigs previously sensitized to ovalbumin. Depleting CD8+ T cells prevented virus-induced M2R dysfunction and hyperreactivity in sensitized animals, but not in nonsensitized animals. Sensitization increased the number of eosinophils in close relation to the airway nerves where, when activated, they release major basic protein, which binds to and blocks the M2Rs. Regardless of sensitization, viral infection decreased the number of visible tissue eosinophils, likely reflecting eosinophil degranulation via cytolysis. Depleting CD8+ T cells prevented this virus-induced eosinophil degranulation. In addition, an antiviral effect of sensitization, which we previously showed to be eosinophil mediated, was again seen. This was prevented by depletion of CD8+ Tcells. Thus, CD8+ T cells play a role in airway hyperreactivity and M2R dysfunction of sensitized virus-infected guinea pigs by mediating eosinophil degranulation near airway nerves. In contrast, CD8+ T cells are not necessary for virus-induced hyperreactivity and M2R dysfunction in nonsensitized guinea pigs.",
author = "Adamko, {Darryl J.} and Allison Fryer and Bochner, {Bruce S.} and David Jacoby",
year = "2003",
month = "2",
day = "15",
language = "English (US)",
volume = "167",
pages = "550--556",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "4",

}

TY - JOUR

T1 - CD8+ T lymphocytes in viral hyperreactivity and M2 muscarinic receptor dysfunction.

AU - Adamko, Darryl J.

AU - Fryer, Allison

AU - Bochner, Bruce S.

AU - Jacoby, David

PY - 2003/2/15

Y1 - 2003/2/15

N2 - In the airways, inhibitory M2 muscarinic receptors (M2Rs) on parasympathetic nerves limit acetylcholine release. Viral infection causes M2R dysfunction, which increases acetylcholine release and leads to airway hyperreactivity. In these studies we tested the role of CD8+ T cells in parainfluenza virus-induced hyperreactivity and M2R dysfunction in normal guinea pigs and in guinea pigs previously sensitized to ovalbumin. Depleting CD8+ T cells prevented virus-induced M2R dysfunction and hyperreactivity in sensitized animals, but not in nonsensitized animals. Sensitization increased the number of eosinophils in close relation to the airway nerves where, when activated, they release major basic protein, which binds to and blocks the M2Rs. Regardless of sensitization, viral infection decreased the number of visible tissue eosinophils, likely reflecting eosinophil degranulation via cytolysis. Depleting CD8+ T cells prevented this virus-induced eosinophil degranulation. In addition, an antiviral effect of sensitization, which we previously showed to be eosinophil mediated, was again seen. This was prevented by depletion of CD8+ Tcells. Thus, CD8+ T cells play a role in airway hyperreactivity and M2R dysfunction of sensitized virus-infected guinea pigs by mediating eosinophil degranulation near airway nerves. In contrast, CD8+ T cells are not necessary for virus-induced hyperreactivity and M2R dysfunction in nonsensitized guinea pigs.

AB - In the airways, inhibitory M2 muscarinic receptors (M2Rs) on parasympathetic nerves limit acetylcholine release. Viral infection causes M2R dysfunction, which increases acetylcholine release and leads to airway hyperreactivity. In these studies we tested the role of CD8+ T cells in parainfluenza virus-induced hyperreactivity and M2R dysfunction in normal guinea pigs and in guinea pigs previously sensitized to ovalbumin. Depleting CD8+ T cells prevented virus-induced M2R dysfunction and hyperreactivity in sensitized animals, but not in nonsensitized animals. Sensitization increased the number of eosinophils in close relation to the airway nerves where, when activated, they release major basic protein, which binds to and blocks the M2Rs. Regardless of sensitization, viral infection decreased the number of visible tissue eosinophils, likely reflecting eosinophil degranulation via cytolysis. Depleting CD8+ T cells prevented this virus-induced eosinophil degranulation. In addition, an antiviral effect of sensitization, which we previously showed to be eosinophil mediated, was again seen. This was prevented by depletion of CD8+ Tcells. Thus, CD8+ T cells play a role in airway hyperreactivity and M2R dysfunction of sensitized virus-infected guinea pigs by mediating eosinophil degranulation near airway nerves. In contrast, CD8+ T cells are not necessary for virus-induced hyperreactivity and M2R dysfunction in nonsensitized guinea pigs.

UR - http://www.scopus.com/inward/record.url?scp=0037441915&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037441915&partnerID=8YFLogxK

M3 - Article

C2 - 12411283

AN - SCOPUS:0037441915

VL - 167

SP - 550

EP - 556

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 4

ER -