title: 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-1beta 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 beta(2)-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.
authors.affiliation: Laboratory of Integrative Physiology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, Japan. y-hayashi@baika.ac.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kannan-Hayashi
authors.forename: Kensaku
authors.initials: K
authors.lastname: Okamura
authors.forename: Shizuka
authors.initials: S
authors.lastname: Hattori
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.forename: Etsuko
authors.initials: E
authors.lastname: Higuchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Terayama
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Moriyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Mukamoto
authors.forename: Masaji
authors.initials: M
authors.lastname: Okada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ohsugi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D007377:Interleukin-3 / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D016501:Neurites / Q000276:immunology*; D009474:Neurons / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000294:innervation* / Q000378:metabolism; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000906:Antibodies; D016207:Cytokines; D007377:Interleukin-3; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside