Cited by 1,025Neuropeptides and Animal PhysiologyVagus Nerve Stimulation ResearchT-cell and B-cell Immunology

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Noradrenergic and peptidergic innervation of lymphoid tissue

Felten, D L, Felten, S Y, Carlson, S L, Olschowka, J A, Livnat, S·1985·The Journal of Immunology

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Abstract

Sympathetic noradrenergic nerve fibers innervate both the vasculature and parenchymal fields of lymphocytes and associated cells in several lymphoid organs, including the thymus, spleen, lymph nodes, gut-associated lymphoid tissue (GALT), and bone marrow, in a variety of mammalian species. This innervation is both regional and specific, and generally is directed into zones of T lymphocytes and plasma cells rather than into nodular regions or B lymphocyte regions. In the thymus, noradrenergic fibers enter with nerve bundles and plexuses around blood vessels, travel into the cortex from subcapsular plexuses and with the vasculature, and branch into the parenchyma of the thymic cortex. The vasculature and parenchymal regions of both the outer and deep cortex are innervated by these fibers. In the spleen, noradrenergic fibers enter with the vasculature, travel along the trabeculae and along the branching vasculature, and are distributed mainly in the white pulp along the central artery and associated periarterial lymphatic sheath. Fibers branch from a dense plexus around the central artery and travel into the parenchyma, where they end among fields of lymphocytes and other cell types. In lymph nodes, noradrenergic fibers enter at the hilus, travel along the vasculature and in a subcapsular plexus, and branch into the parenchyma in paracortical and cortical regions, where they end among lymphocytes. In the GALT, represented in these studies by rabbit appendix, sacculus rotundus, and Peyer’s patches, noradrenergic fibers enter at the serosal surface, travel longitudinally with the muscularis interna, turn radially into internodular plexuses, plunge directly through the thymus-dependent zones, and ramify profusely among lymphocytes, enterochromaffin cells, and plasma cells in the interdomal regions. In the bone marrow, noradrenergic fibers enter with blood vessels, distribute deeply into the marrow on those vessels, and branch sparsely into the substance of the marrow. Immunocytochemical observations revealed the presence of neuro-peptide-like immuno-reactivity in the thymus and spleen. Vasoactive intestinal peptide (VIP)-like immunoreactivity is found in varicose profiles in the thymus within the cortex. In the spleen, immunoreactive profiles showing neuropeptide Y-like, Met-enkephalin-like, cholecystokinin-8 (CCK)-like, and neurotensin-like immunoreactivity are present along the central artery of the white pulp and its smaller branches, with only sparse fibers of most of these peptides entering the parenchyma. CCK-like profiles are present in abundance in the white pulp among parenchymal elements. The presence of noradrenergic innervation and possible peptidergic innervation of a variety of lymphoid tissues suggests that these nerves may serve as an important link between the nervous system and elements of the immune system. Neural modulation of immune responses could utilize a number of possible mechanisms to influence the function of individual cells. Resolution of these mechanisms will require both in vitro testing of individual transmitters or modulators singly and in combination, and in vivo studies that take into account the local microenvironment and temporal influences of hormones and transmitters on specific cell types.

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“…called vasoactive intestinal peptide (VIP) with ≈1 nM Kd (Gaudin et al., 1996), and its neuronal source is derived from neurons in the central nervous system (Lorén et al., 1979), and peripheral neurons that deliver this ligand to numerous organs (Felten et al., 1985; Ottaway © 2011 Elsevier B.V.”
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Adrenocorticotropic hormone as a potential enhancer of T-lymphocyte function in the rat mixed lymphocyte reaction.
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Neuroendocrine Cells within Immune Tissues
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Changes in the content of neuropeptides in intestinal lymph nodes of pigs suffering from experimental Brachyspira hyodysenteriae infection
Łakomy, M., Winnicka, A., Wa̧sowicz, K., Żmudzki, J., Kaleczyc, J., Sienkiewicz, W., & Podlasz, P. (2009) · Veterinární Medicína · doi:10.17221/98/2009-vetmed · Cited by 5
“As results from to-date studies on the porcine lymph nodes, also intestinal ones, they are supplied with adrenergic nerve fibers which contain also NPY and VIP, as well as with sensory nerve terminals which express SP and CGRP (Fink and Weihe, 1988).”
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Mothers with AIDS
Antoni, M. H., Schneiderman, N., LaPerriere, A. R., et al. (1992) · Springer eBooks · doi:10.1007/978-1-4899-2347-9_4 · Cited by 5
Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice
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“The spleen is one of the main reservoirs of FV replication and densely innervated by sympathetic nerve fibers (Felten et al., 1985).”
Background
Immunotoxicology of anticholinesterase agents
Sharma, R. P., & Tomar, R. S. (1992) · Elsevier eBooks · doi:10.1016/b978-0-7506-0271-6.50026-7 · Cited by 5
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“NA fibers abundantly innervate the central artery and its branches and extend into the parenchyma of the periarteriolar lymphatic sheath (PALS) (Williams et al. 1981; Felten et al. 1985; Livnat et al. 1985); they also contact vascular smooth muscle and identified parenchymal cells, including subsets of lymphocytes and…”
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“Numerous morphological observations show the existence of close anatomical localization between sensory nerves and mast cells in skin [2], thymus [25], spleen [10], lung [2] and jejunum [19] indicating a direct communication between mast cells and sensory nerves.”
Background
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Shipman, J. L., Guy, J. S., & Abumrad, N. N. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000081547.31084.23 · Cited by 5
“The major immunoregulatory organs have immense autonomic innervations (70).”
Background

Authors: Felten, D. L., Felten, S. Y., Carlson, S. L., Olschowka, J. A., & Livnat, S.
Affiliations: University of Rochester Medicine (US)
ORCID: Carlson, S L
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 1985-08-01
Volume: 135
Issue: 2
Pages: 755-765
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.135.2.755
OpenAlex: W79466244
Cited by: 1,025
References: 0
Citations by year: 2026: 15 · 2025: 13 · 2024: 15 · 2023: 17 · 2022: 23 · 2021: 23 · 2020: 13 · 2019: 21 · 2018: 26 · 2017: 12 · 2016: 23 · 2015: 16 · 2014: 22 · 2013: 20 · 2012: 24
FWCI: 12.00
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: noradrenergic innervation, sympathetic nerve fibers, lymphoid tissue, thymus, spleen, lymph nodes, gut-associated lymphoid tissue, bone marrow, vasoactive intestinal peptide, neuropeptide Y, substance P, neurokinin-1 receptor, neurokinin-2 receptor, neurokinin-3 receptor, neurotensin, substance P antagonist
MeSH terms: Adrenergic Fibers, Animals, Appendix, Bone Marrow, Intestines, Lymph Nodes, Lymphocytes, Lymphoid Tissue, Nerve Tissue Proteins, Norepinephrine, Rabbits, Spleen, Thymus Gland, Neurotransmitter Agents, Mice, Rats

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Noradrenergic and peptidergic innervation of lymphoid tissue

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