T lymphocytes affect the development of sympathetic innervation of mouse spleen

Besedovsky, Hugo O.; Rey, Adriana del; Sorkin, E.; Burri, Roland; Honegger, C. G.; Schlumpf, Margret; Lichtensteiger, W.

doi:10.1016/0889-1591(87)90020-1

Cited by 32 publications

(30 citation statements)

References 13 publications

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“…2A). Splenic NA concentration in 1-wk-old B6 mice was reduced relative to the first day of life, confirming our previous results in another strain of normal mice (13). No comparable decrease was observed at this age in lpr/lpr mice, in which splenic NA concentration was even higher than at birth (Fig.…”

Section: Ontogeny Of Splenic Noradrenergic Innervation In Lpr/lpr Micesupporting

confidence: 80%

The Role of Noradrenergic Nerves in the Development of the Lymphoproliferative Disease in Fas-Deficient, lpr/lpr Mice

Rey¹,

Roggero²,

Kabiersch

et al. 2006

The Journal of Immunology

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Lpr/lpr mice develop a lymphoproliferative, autoimmune, lupus-like disease. These mice lack functional Fas (CD95) expression and are resistant to Fas ligand (CD178)-mediated apoptosis, a critical mechanism for the maintenance of peripheral tolerance. In this study, we show that noradrenaline (NA), the main sympathetic neurotransmitter, can induce apoptosis of lymphoid cells independently of functional Fas. Based on this finding, we used lpr/lpr mice as model to study the role of noradrenergic nerves in the expression of a lymphoproliferative disease. Early in ontogeny, the concentration of NA was significantly increased in the spleen of lpr/lpr mice, compared with normal littermates. However, splenic sympathetic innervation gradually declined as the disease progressed, and IgM blood levels and splenic NA concentration inversely correlated when the disease was overtly manifested. When the loss of noradrenergic fibers that occurred naturally during adult life in lpr/lpr mice was experimentally advanced by neonatal sympathectomy, the concentration of IgM and IgG2a in blood was markedly higher than that of control lpr/lpr mice, and the appearance of lymphadenopathy was accelerated. Furthermore, although neonatal denervation did not affect the life span of normal animals, it shortened significantly the survival time of lpr/lpr mice. These data show that, in addition to defects in the Fas pathway, an altered sympathetic innervation in lpr/lpr mice also contributes to the pathogenesis of the autoimmune disease, and strongly support the hypothesis that the sympathetic nervous system can modulate the expression of lymphoproliferative diseases.

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Section: Ontogeny Of Splenic Noradrenergic Innervation In Lpr/lpr Micesupporting

confidence: 80%

The Role of Noradrenergic Nerves in the Development of the Lymphoproliferative Disease in Fas-Deficient, lpr/lpr Mice

Rey¹,

Roggero²,

Kabiersch

et al. 2006

The Journal of Immunology

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“…In the rat spleen, NA innervation primarily develops postnatally [90][91]. The splenic nerve enters the spleens as perivascular plexuses coursing along the splenic artery, in the splenic capsule and trabeculae in the mature animal [7,29,43,[92][93][94]. NA nerves in vascular and trabecular plexuses continue into the white pulp primarily associated with the central arterioles and their branches.…”

Section: The Spleenmentioning

confidence: 99%

“…The thymus of young adult animals is richly innervated by the SNS [29][30][31][32][33][34][35][36][37][38]. Thymic NA nerves originate primarily from the superior cervical and stellate ganglia [30,39,40].…”

Section: Sympathetic Neurotransmission In the Thymusmentioning

confidence: 99%

Sympathetic modulation of immunity: Relevance to disease

Bellinger

Millar

Perez

et al. 2008

Cellular Immunology

227

185

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Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease-or injury-induced 'fight' responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.

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“…Besedovsky et al (29) showed that athymic nude mice had increased noradrenaline levels and fluorescent catecholamine-containing nerve fibers in their spleen compared with normal littermates. In contrast, reduced noradrenaline levels and nerve destruction were reported in the spleen of MRL-lpr/lpr mice or AIDS mice: the former animal served as a genetic model of systemic lupus erythematosus, a disease in which the number of CD4 Ϫ /CD8 Ϫ T cells is increased, and the latter is characterized by the rapid and profound lymphoproliferation and dysregulation of cytokine production accompanied by hypergammaglobulinemia and immunosuppression (30,31).…”

Section: Discussionmentioning

confidence: 99%

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

Kannan-Hayashi

Okamura

Hattori

et al. 2008

The Journal of Immunology

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To determine the role played by lymphocytes and cytokines in the growth of sympathetic neurons in vivo, the innervation and cytokine levels were examined in the spleens of SCID mice that lack T and B cells. Splenic noradrenaline, nerve growth factor (NGF), and IL-1β levels were elevated in SCID mice. Immunohistochemical examination revealed that the density of tyrosine hydroxylase-positive (TH+) fibers of splenic central arteries in SCID mice was increased compared with wild-type C.B-17 mice, while SCID mice had significantly fewer TH+ fibers in their periarteriolar lymphatic sheaths (PALS). Two weeks after SCID mice were injected with C.B-17 splenic T cells, their TH+ fiber staining increased in the PALS. IL-3 levels increased significantly in SCID mice following T cell reconstitution, and the administration of anti-IL-3 Ab blocked the above T cell-induced increase in innervation in the PALS. Anti-IL-3 treatment also inhibited the regeneration of splenic sympathetic neurons in C.B-17 mice after they were chemically sympathetomized with 6-hydroxydopamine. Depletion of NK cells by anti-asialo GM1 promoted the splenic innervation in SCID mice, while there were no significant changes in the innervation between CD8+ T cell-deficient β2-microglobulin knockout mice and their wild type. Our results suggest that T cells (probably CD4+ Th cells but not CD8+ CTLs) play a role in regulating the sympathetic innervation of the spleen; this effect appeared to be mediated, at least in part, by IL-3. On the contrary, NK cells may exert an inhibitory effect on the sympathetic innervation.

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T lymphocytes affect the development of sympathetic innervation of mouse spleen

Cited by 32 publications

References 13 publications

The Role of Noradrenergic Nerves in the Development of the Lymphoproliferative Disease in Fas-Deficient, lpr/lpr Mice

The Role of Noradrenergic Nerves in the Development of the Lymphoproliferative Disease in Fas-Deficient, lpr/lpr Mice

Sympathetic modulation of immunity: Relevance to disease

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

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