[通过多次静脉注射供体脾细胞诱导对心脏同种异体移植物的耐受性]
[Induced tolerance to cardiac allografts with multiple intravenous injection of donor spleen cells].
作者信息
Guo Hong-Wei, Wu Qing-Yu, Xie Shu-Sheng, Zhang Qing-Yin, Yang Xiu-Bin, Shao Meng-Ping
机构信息
Department of Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
出版信息
Zhonghua Wai Ke Za Zhi. 2004 Jun 7;42(11):664-7.
OBJECTIVE
To study the methods and mechanisms of immune tolerance in cardiac transplantation.
METHODS
Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into five groups: untreated, intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat, intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat, multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide, 11 days later heart transplantation was performed. Mean survival time (MST), histological changes, mixed lymphocyte reaction (MLR), the role of interleukin-2 (IL-2) to MLR and the role of tolerant rat splenocytes to MLR were measured after operation.
RESULTS
The survival time of heart allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide [MST: (85.3 +/- 7.5) d, t = 0, P < 0.01] was significantly longer than in the groups of untreated [MST: (7.3 +/- 1.0) d], intravenous injection of 1 x 10(8) DA splenocytes to Lewis rat [MST: (7.9 +/- 0.9) d], intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (8.1 +/- 1.2) d], intravenous injection of 1 x 10(8) DA splenocytes combined with intraperitoneal injection of cyclophosphamide (100 mg/kg) to Lewis rat [MST: (25.8 +/- 3.5) d]. Only a few inflammatory cells infiltrated in cardiac allografts in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide. MLR in the group of multiple injection of DA rat splenocytes with intraperitoneal injection of cyclophosphamide were significantly decreased compared with those of normal control (t = 0, P < 0.01). IL-2 could partly reversed the hyporesponsiveness of MLR in tolerant rats, the tolerance could be transferred in vitro.
CONCLUSIONS
Multiple injection of donor splenocytes combined with intraperitoneal injection of cyclophosphamide to recipients could induce immune tolerance to cardiac allografts.
目的
研究心脏移植免疫耐受的方法及机制。
方法
采用Ono模型将雄性DA大鼠心脏移植到雄性Lewis大鼠体内，随机分为五组：未处理组；向Lewis大鼠静脉注射1×10⁸个DA脾细胞；向Lewis大鼠腹腔注射环磷酰胺（100mg/kg）；向Lewis大鼠静脉注射1×10⁸个DA脾细胞并联合腹腔注射环磷酰胺（100mg/kg）；多次注射DA大鼠脾细胞并腹腔注射环磷酰胺，11天后进行心脏移植。术后测量平均存活时间（MST）、组织学变化、混合淋巴细胞反应（MLR）、白细胞介素-2（IL-2）对MLR的作用以及耐受大鼠脾细胞对MLR的作用。
结果
多次注射DA大鼠脾细胞并腹腔注射环磷酰胺组心脏异体移植的存活时间[MST：（85.3±7.5）天，t = 0，P < 0.01]明显长于未处理组[MST：（7.3±1.0）天]、向Lewis大鼠静脉注射1×10⁸个DA脾细胞组[MST：（7.9±0.9）天]、向Lewis大鼠腹腔注射环磷酰胺（100mg/kg）组[MST：（8.1±1.2）天]、向Lewis大鼠静脉注射1×10⁸个DA脾细胞并联合腹腔注射环磷酰胺（100mg/kg）组[MST：（25.8±3.5）天]。多次注射DA大鼠脾细胞并腹腔注射环磷酰胺组心脏异体移植中仅有少量炎性细胞浸润。多次注射DA大鼠脾细胞并腹腔注射环磷酰胺组的MLR与正常对照组相比明显降低（t = 0，P < 0.01）。IL-2可部分逆转耐受大鼠MLR的低反应性，这种耐受性可在体外转移。
结论
多次向受体注射供体脾细胞并联合腹腔注射环磷酰胺可诱导对心脏异体移植的免疫耐受。
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