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

Abstract

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.

Nasal IgA secretion in a murine model of acute stress. The possible role of catecholamines.

“…The mice were inoculated intraperitoneally with phentolamine (15 mg/kg) and nadolol (5 mg/kg) 30 min before the stress protocol. Control animals were inoculated with sterile PBS only (Eijkelkamp et al, 2007;Kannan-Hayashi et al, 2008).…”

The Neurology of the Immune System: Neural Reflexes Regulate Immunity

“…SCID mice, which lack functional B and T cells, have increased numbers of nerve endings around central arteries and reduced numbers in the white pulp parenchyma of spleen. Adoptive transfer of T cells restores the normal pattern through a mechanism dependent in part on IL-3 release, indicating that immune cells modulate neural network formation (Kannan-Hayashi et al, 2008). Nude mice, which lack functional T cells, have a higher density of nerve fibers in spleen, and adoptive transfer of T cells into these mice reduces spleen catecholaminergic load (Besedovsky et al, 1987).…”