Autonomic innervation of immune organs and neuroimmune modulation

Abstract

1. Increasing evidence indicates the occurrence of functional interconnections between immune and nervous systems, although data available on the mechanisms of this bi-directional cross-talking are frequently incomplete and not always focussed on their relevance for neuroimmune modulation. 2. Primary (bone marrow and thymus) and secondary (spleen and lymph nodes) lymphoid organs are supplied with an autonomic (mainly sympathetic) efferent innervation and with an afferent sensory innervation. Anatomical studies have revealed origin, pattern of distribution and targets of nerve fibre populations supplying lymphoid organs. 3. Classic (catecholamines and acetylcholine) and peptide transmitters of neural and non-neural origin are released in the lymphoid microenvironment and contribute to neuroimmune modulation. Neuropeptide Y, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide represent the neuropeptides most involved in neuroimmune modulation. 4. Immune cells and immune organs express specific receptors for (neuro)transmitters. These receptors have been shown to respond in vivo and/or in vitro to the neural substances and their manipulation can alter immune responses. Changes in immune function can also influence the distribution of nerves and the expression of neural receptors in lymphoid organs. 5. Data on different populations of nerve fibres supplying immune organs and their role in providing a link between nervous and immune systems are reviewed. Anatomical connections between nervous and immune systems represent the structural support of the complex network of immune responses. A detailed knowledge of interactions between nervous and immune systems may represent an important basis for the development of strategies for treating pathologies in which altered neuroimmune cross-talking may be involved.

Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity

“…Our results indicate that Ag recognition by naive CD4 + T cells induces DRD3 expression, rendering this population sensible to this neurotransmitter during the activation/differentiation process. In a physiologic context, DRD3 expressed on recently activated CD4 + T cells may be stimulated by DA released by neighboring dendritic cells present in the lymph node, or by sympathetic dopaminergic terminals reported to innervate both primary and secondary lymphoid organs (32)(33)(34). The latter option seems the most likely, considering that we detect DRD3 expression on CD4 + T cells between 2 and 3 d after activation and that studies using intravital microscopy have shown that in vivo-activated CD4 + T cells reduce their interaction with dendritic cells after 40 h of residence in the lymph node (35).…”

Incidence of acute hepatitis B in patients with spinal cord injury

“…Decentralization of autonomic system to lymphoid organs including spleen may be an important factor in disruption of immune response. 6 SCI patients may have muted neutrophil phagocytosis, natural killer cell cytotoxicity and T-lymphocyte activation compared with healthy controls. 7 Furthermore, degree of reduced phagocytosis and impaired B-cell functions may be correlated with level of SCI injury.…”

Neuritogenic Effects of T Cell-Derived IL-3 on Mouse Splenic Sympathetic Neurons In Vivo

“…B cells were purified by negative selection using a mouse B cell enrichment mixture (StemCell Technologies) that contained Abs directed against mouse CD4, CD8, CD11b, myeloid differentiation Ag Gr-1, and erythroid Ag TER 119, as well as dense particles that were covalently coated with a second Ab. B cell purity was found to be Ͼ90%, which was confirmed by immunocytochemistry using HRP-labeled sheep anti-mouse IgG F(abЈ) 2 (1/100 dilution; Amersham Biosciences). Cell viability in both cases was found to be Ͼ85% as assessed by the trypan blue exclusion test.…”

“…Two weeks later, immunohistochemistry was performed on the spleens of these animals using anti-CD3, anti-IgG F(abЈ) 2 , and TH Abs. FACS analysis was also performed using splenic cells prepared as mentioned above.…”

“…E vidence suggests the existence of an important functional link between the nervous and immune systems (1,2). Primary and secondary lymphoid organs are well-innervated by sympathetic efferents, and their neurotransmitter noradrenaline was reported to modulate a variety of immune functions by binding to adrenergic receptors on immune cells (3)(4)(5)(6).…”