Bond Gregor, Nowocin Anna, Sacks Steven H, Wong Wilson
MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's and St Thomas' Hospitals, London, UK.
MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's and St Thomas' Hospitals, London, UK.
Transpl Immunol. 2015 Jan;32(1):40-5. doi: 10.1016/j.trim.2014.10.004. Epub 2014 Oct 18.
After inflammatory stimulus, mast cells (MC) migrate to secondary lymphoid organs contributing to adaptive immune response. There is growing evidence that MC also contribute to transplant tolerance, but little is known about MC kinetics in the setting of transplant tolerance and rejection. Likewise it has been demonstrated that complement split products, which are known to act as chemoattractants for MC, are necessary for transplant tolerance.
Naive skin and lymph nodes, skin grafts and draining lymph nodes from wild type and complement deficient mice treated with a tolerogenic protocol were analyzed.
Early after tolerance induction MC leave the graft and migrate to the draining lymph nodes. After this initial efflux, MC reappear in tolerant skin grafts in numbers exceeding that of naive skin. MC density in draining lymph nodes obtained from tolerant mice also increased post transplant. There was no difference in MC density, migration and degranulation status between wild type and complement deficient mice implicating that chemotaxis is not disturbed in complement deficient mice.
This study gives detailed insight in kinetics of MC migration during transplant tolerance induction and rejection providing further evidence for a role of MC in transplant tolerance.
在炎症刺激后,肥大细胞(MC)迁移至次级淋巴器官,促进适应性免疫反应。越来越多的证据表明,MC也有助于移植耐受,但对于移植耐受和排斥反应情况下MC的动力学了解甚少。同样,已知作为MC趋化因子的补体裂解产物对于移植耐受是必需的。
分析了用致耐受性方案处理的野生型和补体缺陷小鼠的未致敏皮肤和淋巴结、皮肤移植物及引流淋巴结。
在诱导耐受后早期,MC离开移植物并迁移至引流淋巴结。在这一初始外流之后,MC重新出现在耐受皮肤移植物中,其数量超过未致敏皮肤。移植后,从耐受小鼠获得的引流淋巴结中的MC密度也增加。野生型和补体缺陷小鼠之间的MC密度、迁移和脱颗粒状态没有差异,这表明补体缺陷小鼠的趋化作用未受干扰。
本研究详细揭示了移植耐受诱导和排斥反应期间MC迁移的动力学,为MC在移植耐受中的作用提供了进一步证据。