Sympathetic nervous system control of anti-influenza CD8⁺T cell responses

Abstract

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 crosspriming. 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 ␤2 (but not ␤1 or ␣) 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 ␤-blockers, one of the most widely prescribed classes of drugs.antigen presentation ͉ vaccine ͉ cross-priming ͉ direct-priming ͉ dendritic cell

Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes

“…As sentinels for damaged tissue and invading pathogens, APCs have also evolved a central role in the activation and guidance of T and B lymphocytes as they mount more complex adaptive immune responses (15,23). Bidirectional dendritic cell regulation by social adversity is consistent with previous neural manipulation studies (33) showing a redirection of T lymphocytes away from "T-helper 1" (Th1) responses effective against viruses and other intracellular pathogens and toward Th2 responses targeting extracellular pathogens, such as bacteria (11,15,23). Monocytes and dendritic cells also orchestrate the longterm trophic development, maintenance, and repair of healthy tissue and incidentally contribute to cancer development and metastasis in the process (26,27).…”

Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI

“…produced an 84% decrease in splenic norepinephrine 40 and has been used in numerous studies, contributing to what is now a large body of evidence demonstrating an interaction between the sympathetic nervous system and immune function. [41][42][43] In our studies, splenic denervation via splenic injections of 6-OHDA completely abolished the protective effect of ultrasound in IRI, strongly suggesting that ultrasound reduces IRI in a catecholaminergic-dependent and presumably splenic nerve-dependent manner. The immune modulatory effect of splenic chemical sympathectomy produced by systemic administration of 6-OHDA, increased splenocyte proliferation and cytokine production, was blocked by pretreating animals with desipramine, a norepinephrine reuptake inhibitor that blocks uptake of 6-OHDA into nerve terminals, suggesting that the effects of 6-OHDA were mediated neuronally.…”

Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells Potentiates Th17-Mediated Immunity

“…Traditionally, it has been thought that the functions of immune cells such as T cells and DCs are regulated mainly by cytokines. However, a number of more recent studies have shown that immune system cells can also be regulated by neurotransmitters (6)(7)(8)(9)(10)(11). Consistent with this, both primary and secondary lymphoid organs are highly innervated by sympathetic ends that store dopamine (DA) (12,13).…”