摘要
目的比较分析同种异体与异种骨移植后的免疫反应,观察IL-4和IL-10对免疫反应的影响。方法取C57BL/6小鼠和新西兰兔作为同种异体和异种骨供体,分别制成新鲜骨和冻干骨。于股后肌袋内分别植入新鲜同种异体、新鲜异种、新鲜异种(给予IL-4和IL-10治疗)、冻干同种异体及冻干异种骨。结果在植入新鲜骨的各组中,新鲜异种组早期细胞刺激反应较新鲜同种组强(P< 0.05)。1周时新鲜异种组CD4+ T细胞亚群和CD4/CD8比值与新鲜同种组间差异无显著性,但2周时明显低于新鲜同种组。细胞因子检测显示,新鲜异种组的IL-2分泌较新鲜同种组多(P< 0.05),而且IFN-γ分泌少,IL-4分泌多(P<0.05)。组织学检查发现,新鲜异种组细胞浸润多,且以单核、巨噬细胞为主。与新鲜异种组相比,用IL-4和IL-10治疗后明显抑制了骨抗原二次刺激引起的细胞增殖(P<0.01);早期IFN-γ分泌增加,2周时IFN-γ和IL-4分泌均明显减少(P<0.05);组织学检查显示,注射IL-4和IL-10后植骨处局部炎细胞浸润减少,诱导成骨增多。而在植入冻干骨的各组中,冻干异种组的细胞刺激反应始终比冻干同种组强(P<0.05),而且其CD4+和CD8+T细胞亚群及IL-2分泌均高于同种异体组(P<0.05)。结论新鲜异种骨移植早期排斥反应强、后期弱,早期以Th2反应为主。
Objective To investigate the rejection mechanisms of bone grafts by comparing the immune reaction of xenografts versus allografts, and the influence of IL-4 and IL-10 on immune responses. Methods Twenty C57BL/6 mice and 1 New Zealand rabbit were used as transplant donors for allografts and xenografts, respectively. One hundred BALB/c mice were used as transplant recipients and randomly divided into 5 groups. Using a model of the muscle pouch for implantation, the immune reactions of bone allografts and bone xenografts were studied through observing the lymphocyte responses of the stimulating index of lymphocytes from the mixed lymphocyte culture (MLC), subsets of lymphocyte, cytokinetic and histological findings in 1, 2, 4 and 6 weeks after implantation respectively. Results Xenograft rejection was rapid (1 week) and stronger than allograft rejection (P< 0.05), it involved predominantly CD4+ T cells and exhibited secretion for Th2 cytokines (IL-4) (P< 0.05) at an early stage. However, allograft rejections were prolonged (2-3 weeks), characterized by infiltrating CD4+ T and CD8+ T cells and associated with a Th1-type cell response (IFN-γ). Histological analysis showed that bone xenografts were infiltrated mainly by monocytes and macrophages. Nevertheless, the rejection response of freeze-dried bone xenografts was prolonged, and more pronounced than that of freeze-dried bone allografts (P< 0.05), it consisted of infiltrating CD4+ T and CD8+ T cells (P< 0.05) at all the periods. Compared with that of fresh bone xenografts rejection , the lymphocyte proliferation of the second stimulation was significantly inhibited in treatment groups (IL-4 + IL-10) (P< 0.01), and associated with an elevated Th1 cytokines (IFN-γ) at an early stage (1 week) and a general reduction both in IFN-γ and in IL-4 at two weeks (P< 0.05). From histological observation, inflammatory cell infiltration was decreased, more cartilage and new bone were developed in the treatment group. Conclusion The xenograft rejection is stronger than that of allograft, especially at an early stage. The rejection of xenograft is mainly associated with a Th2-type cell response, whereas the allograft with a Th1-type.
出处
《中华骨科杂志》
CAS
CSCD
北大核心
2004年第10期609-614,共6页
Chinese Journal of Orthopaedics
基金
国家自然科学基金资助项目(30070758)
关键词
同种异体
异种骨移植
免疫反应
比较研究
Bone transplantation
Immunoassay
Transplantation, heterologous
