Kannan-Hayashi Yukiko, Okamura Kensaku, Hattori Shizuka, Kuwamura Mitsuru, Higuchi Etsuko, Terayama Hiroki, Moriyama Mitsuaki, Mukamoto Masafumi, Okada Masaji, Ohsugi Yoshiyuki, Nakamura Yoichi
Laboratory of Integrative Physiology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, Japan.
J Immunol. 2008 Mar 15;180(6):4227-34. doi: 10.4049/jimmunol.180.6.4227.
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.
为了确定淋巴细胞和细胞因子在体内交感神经元生长中所起的作用，我们检测了缺乏T细胞和B细胞的SCID小鼠脾脏中的神经支配和细胞因子水平。SCID小鼠脾脏中的去甲肾上腺素、神经生长因子（NGF）和白细胞介素-1β水平升高。免疫组织化学检查显示，与野生型C.B-17小鼠相比，SCID小鼠脾脏中央动脉中酪氨酸羟化酶阳性（TH(+)）纤维的密度增加，而SCID小鼠动脉周围淋巴鞘（PALS）中的TH(+)纤维明显较少。给SCID小鼠注射C.B-17脾脏T细胞两周后，其PALS中的TH(+)纤维染色增加。T细胞重建后，SCID小鼠体内的IL-3水平显著升高，抗IL-3抗体的给药阻断了上述T细胞诱导的PALS中神经支配的增加。抗IL-3治疗还抑制了C.B-17小鼠经6-羟基多巴胺化学去交感神经后脾脏交感神经元的再生。抗唾液酸GM1耗尽NK细胞促进了SCID小鼠的脾脏神经支配，而CD8(+) T细胞缺陷的β2-微球蛋白敲除小鼠与其野生型之间的神经支配没有显著变化。我们的结果表明，T细胞（可能是CD4(+) Th细胞而非CD8(+) CTL）在调节脾脏的交感神经支配中起作用；这种作用似乎至少部分由IL-3介导。相反，NK细胞可能对交感神经支配发挥抑制作用。
