Tanzola Melinda B, Robbie-Ryan Michaela, Gutekunst Claire Anne, Brown Melissa A
Graduate Program in Immunology and Molecular Pathogenesis, Emory University School of Medicine, Atlanta, GA 30322, USA.
J Immunol. 2003 Oct 15;171(8):4385-91. doi: 10.4049/jimmunol.171.8.4385.
Previous studies using mast cell-deficient mice (W/W(v)) revealed that mast cells influence disease onset and severity of experimental allergic/autoimmune encephalomyelitis (EAE), the murine model for multiple sclerosis. The mast cell populations of these mice can be restored by transferring bone marrow-derived mast cells (BMMCs). Studies using the W/W(v) reconstitution model have lead to major advances in our understanding of mast cell roles in vivo. However, despite its common use, details regarding the sites and kinetics of mast cell repopulation have remained largely uncharacterized. In this study, we examined the kinetics and tissue distribution of green fluorescent protein(+) BMMCs in reconstituted W/W(v) mice to identify sites of mast cell influence in EAE. Reconstitution of naive animals with BMMCs does not restore mast cell populations to all organs, notably the brain, spinal cord, lymph nodes, and heart. Despite the absence of mast cells in the CNS, reconstituted mice exhibit an EAE disease course equivalent to that induced in wild-type mice. Mast cells are found adjacent to T cell-rich areas of the spleen and can migrate to the draining lymph node after disease induction. These data reveal that mast cells can act outside the CNS to influence EAE, perhaps by affecting the function of autoreactive lymphocytes.
以往利用肥大细胞缺陷小鼠(W/W(v))开展的研究表明,肥大细胞会影响实验性变应性/自身免疫性脑脊髓炎(EAE,多发性硬化症的小鼠模型)的疾病发作和严重程度。通过移植骨髓来源的肥大细胞(BMMC)可使这些小鼠的肥大细胞数量得以恢复。利用W/W(v)重建模型开展的研究已使我们对肥大细胞在体内作用的理解取得了重大进展。然而,尽管该模型被广泛应用,但关于肥大细胞重新聚集的部位和动力学的细节在很大程度上仍未得到充分描述。在本研究中,我们检测了绿色荧光蛋白(+)BMMC在重建的W/W(v)小鼠中的动力学和组织分布,以确定肥大细胞在EAE中发挥作用的部位。用BMMC对未接触过抗原的动物进行重建并不能使所有器官的肥大细胞数量恢复正常,尤其是脑、脊髓、淋巴结和心脏。尽管中枢神经系统中没有肥大细胞,但重建后的小鼠表现出与野生型小鼠诱导的EAE病程相当。在脾脏富含T细胞的区域附近可发现肥大细胞,并且在疾病诱导后它们可迁移至引流淋巴结。这些数据表明,肥大细胞可在中枢神经系统外发挥作用以影响EAE,可能是通过影响自身反应性淋巴细胞的功能来实现的。