Published ahead of print on October 31, 2002, doi:10.1164/rccm.200206-506OC Am. J. Respir. Crit. Care Med., Volume 167, Number 4, February 2003, 550-556 A more recent version of this article appeared on February 15, 2003
Submitted on June 4, 2002 CD8+ T-Lymphocytes in Viral Hyperreactivity and M2 Muscarinic Receptor DysfunctionDarryl J Adamko1,1 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada, 2 Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA * To whom correspondence should be addressed. E-mail: djacoby{at}jhmi.edu.
In the airways, inhibitory M2 muscarinic receptors on parasympathetic nerves limit acetylcholine release. Viral infection causes M2 receptor 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 M2 receptor dysfunction in normal guinea pigs and in guinea pigs previously sensitized to ovalbumin. Depleting CD8+ T-cells prevented virus-induced M2 receptor dysfunction and hyperreactivity in sensitized animals, but not non-sensitized 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 M2 receptor. Regardless of sensitization, virus 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+ T-cells. Thus, CD8+ T-cells play a role in airway hyperreactivity and M2 receptor 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 M2 receptor dysfunction in non-sensitized guinea pigs. Key words: T-cells, eosinophils, viral immunity, asthma, airway hyperreactivity
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