It takes nerve to tell T and B cells what to do

Abstract

The existence of an association between the brain and immunity has been documented. Data show that the nervous and immune systems communicate with one another to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity, which in turn, activates output through the peripheral nervous system to regulate the level of immune cell activity and the subsequent magnitude of an immune response. In this review, we will focus our presentation and discussion on the findings that indicate a regulatory role for the peripheral sympathetic nervous system in modulating the level of cytokine and antibody produced during an immune response. Data will be discussed from studies involving the stimulation of the beta2 adrenergic receptor expressed on CD4+ T cells and B cells by norepinephrine or selective agonists. We will also discuss how dysregulation of this line of communication between the nervous and immune systems might contribute to disease development and progression.

Autonomic innervation and regulation of the immune system (1987–2007)

“…The effect of NE-depletion on the primary T cell-dependent antibody response in vivo has also been investigated [reviewed extensively in (Kin and Sanders, 2006;Kohm and Sanders, 2001b;Sanders and Munson, 1985;Sanders and Straub, 2002)]. Data have shown that either a decrease or increase in the Th cell-dependent IgM antibody response occurs after NE depletion.…”

“…Thus, it is difficult to conclude the effect of NE-depletion on the IgM and IgG response in vivo, although most data indicate suppression, suggesting that NE may be needed to play a positive role in an antibody response in vivo, but the mechanisms by which this occurred are beginning to become clearer The finding in vivo that NE-depleted mice were unable to upregulate CD86 expression on B cells when compared to NE-intact mice suggested that CD86 may be regulated by NE to help enhance the antibody response, possibly via co-stimulation of the T cell. But, when examined in vitro, β 2 AR stimulation on a B cell at the time of B cell activation, in the presence or absence of a T cell, directly increased the level of CD86 expressed on, and IgG1 produced by, a B cell [reviewed extensively in (Kin and Sanders, 2006). The β 2 AR-and CD86-induced increase in IgG1 occurred on a per cell basis by increasing the rate of mature IgG1 mRNA production.…”

“…There are two types of receptors that bind NE, namely the alpha-adrenergic receptor (αAR) and the beta-adrenergic receptor (βAR), which are expressed in a tissue-specific manner and exhibit differing affinities for NE. The beta2-adrenergic receptor (β 2 AR) subtype is the primary receptor that is expressed on immune cells in both rodents and humans [reviewed extensively in (Kin and Sanders, 2006;Sanders et al, 2001)]. The number of β 2 ARs expressed on immune cells is variable and is regulated by a number of different factors, including cell activation, cytokines, hormones, and neurotransmitters.…”

“…Early in vitro studies using unfractionated CD4+ T cell populations suggested that NE, β 2 ARselective agonists, or other cAMP-elevating agents either inhibited or enhanced the level of IL-2, IFN-γ, or IL-4 produced, while studies using populations of Th1 and Th2 cells suggested that these agents decreased the level of IFN-γ and increased the level of IL-4, respectively [Reviewed extensively in (Kin and Sanders, 2006;Kohm and Sanders, 2001a;Sanders and Straub, 2002). When naive T cells were isolated and activated, IL-2 secretion was decreased by exposure to NE, suggesting that NE and β 2 AR stimulation affected the ability of an activated naive T cell to expand in number.…”

Serum from exercising humans suppresses t-cell cytokine production

“…Circulating t-cell numbers and function are influenced by brief periods of exercise [6,7], and a number of mechanisms have been proposed to explain these effects. First, as noted, exercise alters circulating factors and mediators (e.g., lactate, IL-6, catecholamines, growth hormone) that can affect t-cells [8][9][10]. Secondly, lymphocytes could be influenced by more direct effects such as exercise associated neurostimulation of lymph nodes and other lymph tissues [11,12].…”