Mechanisms underlying chemical sympathectomy-induced suppression of herpes simplex virus-specific cytotoxic T lymphocyte activation and function.
Lymphoid tissues are extensively innervated by noradrenergic fibers of the sympathetic nervous system. 6-hydroxydopamine (6-OHDA)-induced chemical sympathectomy is commonly used to assess the impact of this innervation on immune function. Using the glucocorticoid receptor antagonist RU486, the mineralocorticoid receptor antagonist spironolactone, and the beta-adrenergic receptor antagonist nadolol, the roles of corticosterone and norepinephrine in sympathectomy-mediated modulation of both the primary and memory cellular immune responses to herpes simplex virus type 1 (HSV-1) infection was investigated. We demonstrated that both of these immunomodulators play a role in mediating sympathectomy-induced suppression of the generation of HSV-specific primary cytotoxic T lymphocytes (CTL) and the activation of HSV-specific memory CTL (CTLm). Furthermore, we demonstrated a role for both Type I and Type II corticosteroid receptors in the regulation of HSV-specific immunity. Overall, these findings not only further support a role for neuroendocrine-mediated modulation of immune function, but also a need to exercise caution in attributing the effects of chemical sympathectomy to solely the absence of sympathetic innervation of lymphoid tissues.
Leo
N A
NA
Department of Microbiology and Immunology (H107), The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
Bonneau
R H
RH
D000818:Animals; D002460:Cell Line; D003345:Corticosterone / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human; D006727:Hormone Antagonists / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D009638:Norepinephrine / Q000276:immunology; D016627:Oxidopamine; D018161:Receptors, Mineralocorticoid / Q000276:immunology; D011987:Receptors, Steroid / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000821:virology; D013563:Sympathectomy, Chemical; D013565:Sympatholytics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*
D006727:Hormone Antagonists; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D013565:Sympatholytics; D015735:Mifepristone; D016627:Oxidopamine; D003345:Corticosterone; D009638:Norepinephrine