供体凋亡／坏死细胞对大鼠脾移植急性排斥反应的作用研究

Opposite effects of donor apoptotic versus necrotic splenocytes on acute rejection in rat spleen transplantation

目的探讨供体凋亡与坏死细胞对大鼠脾移植急性排斥反应的作用及机制。方法建立大鼠异位脾移植模型后，随机分为4组：A组输注生理盐水2ml；B组输注供者凋亡细胞5×10^6；C组输注正常供体细胞悬液5×10^6；D组输注5×10^6坏死细胞。术后不同时间点每组取大鼠8只进行指标测定。结果移植后脾出现排斥反应并逐渐加重，D组最为严重，A组和C组次之，B组最为轻微。各组移植脾匀浆和受体血清中IFN-γ水平逐步增加，为B组低于A组，而D组高于A组，A组与C组相似。B组大鼠移植脾匀浆和血清中TGF-β水平明显升高，其他各组TGF-β1水平持续于较低水平。凋亡细胞抑制混合淋巴细胞反应，而坏死细胞则作用相反。结论供体细胞能够影响大鼠脾移植急性排斥反应，可能与细胞因子偏移和受体同种免疫反应性改变有关。

Objective To determine whether infusion of donor apoptotic and necrotic cells can influence rejection to the allografted spleens and explore its potential mechanism. Methods After establishment of heterotopic spleen transplantation, recipient rats were randomized into 4 groups, each receiving infusion of 2ml physiological saline （Group A）or 5 × 10^6 apoptotic donor cells （Group B） or viable donor cells （Group C） or necrotic donor cells （Group D）. Eight recipient rats in each group were sacrificed on day 1, 4, 7 and 14 after transplantation and histological analysis was performed for the transplanted spleens. Mixed lymphatic reaction and cytokine levels in transplanted spleen homogenate and recipient serum were also determined. Results In excised spleens, pathological changes were the severest in rats of Group D, followed by those of Group A, D and B. Generally, Group A IFN-γ level in spleen homogenate and recipient serum was comparable to that of Group D, but lower than that of Group C and higher than that of Group B at each indicated time point. TGF-β1 level of Group B went up markedly after administration of apoptotic cells but remained around baseline in other groups. Furthermore, apoptotic cells induced hyporesponsiveness of allogeneic splenocytes, whereas necrotic cells caused hyperresponsiveness of allogeneic splenocytes. Conclusions Infusion of donor apoptotic and necrotic cells can influence rejection to the allografted spleens and the potential mechanism might be associated with cytokine shift and changes in recipient allogeneic reactivity.