Sympathetic nervous system control of anti-influenza CD8+ T cell responses.
Despite the longstanding appreciation of communication between the nervous and the immune systems, the nature and significance of these interactions to immunity remain enigmatic. Here, we show that 6-hydroxydopamine-mediated ablation of the mouse peripheral sympathetic nervous system increases primary CD8(+) T cell responses to viral and cellular antigens presented by direct priming or cross-priming. The sympathetic nervous system also suppresses antiviral CD4(+) T cell responses, but this is not required for suppressing CD8(+) T cell responses. Adoptive transfer experiments indicate that enhanced CD8(+) responses do not result from permanent alterations in CD8(+) T cell function in sympathectomized mice. Rather, additional findings suggest that the sympathetic nervous system tempers the capacity of antigen-presenting cells to activate naïve CD8(+) T cells. We also show that antiviral CD8(+) T cell responses are enhanced by administration of a beta(2) (but not beta(1) or alpha) adrenergic antagonist. These findings demonstrate a critical role for the sympathetic nervous system in limiting CD8(+) T cell responses and indicate that CD8(+) T cell responses may be altered in patients using beta-blockers, one of the most widely prescribed classes of drugs.
Grebe
Kristie M
KM
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Hickman
Heather D
HD
Irvine
Kari R
KR
Takeda
Kazuyo
K
Bennink
Jack R
JR
Yewdell
Jonathan W
JW
D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D009975:Orthomyxoviridae / Q000276:immunology*; D016627:Oxidopamine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000276:immunology*
D058672:Adrenergic beta-2 Receptor Antagonists; D016627:Oxidopamine