Specific immunosuppression by mixed chimerism with bone marrow transplantation after Staphylococcal Enterotoxin B pretreatment could prolong corneal allograft survival in mice
Specific immunosuppression by mixed chimerism with bone marrow transplantation after Staphylococcal Enterotoxin B pretreatment could prolong corneal allograft survival in mice
复制标题
葡萄球菌肠毒素 B 预处理后混合嵌合结合骨髓移植的特异性免疫抑制可延长小鼠同种异体角膜移植物的存活
作者：
Zhang, Yingnan;Pan, Zhiqiang;Chen, Yu;Jie, Ying;He, Yan
目的探讨葡萄球菌肠毒素B(SEB)超抗原预处理联合异基因骨髓移植(BMT)诱导免疫抑制状态和抑制小鼠角膜移植排斥反应的效果。方法BALB/C(H-2d)小鼠为骨髓移植和角膜移植供体，C57BL/6(H-2b)小鼠为受体。在骨髓移植前，受者接受SEB、环磷酰胺(CYP)或生理盐水(NS)的单次注射。骨髓移植后7天行同种异体角膜穿透性角膜移植。在骨髓移植后第14、28和56天检测受者的骨髓嵌合体(供者主要组织相容性复合体-II H2-d)。以C57BL/6小鼠的脾细胞为反应物，与C57BL/6(同基因)、BALB/C(同种)或CBA/1(第三方)小鼠的刺激细胞共同培养，用混合淋巴细胞反应(MLR)检测受体免疫应答。检测受体小鼠体内分化4受体阳性(CD4+)和CD8+T细胞的分化情况。用Kaplan-Meier生存曲线评估角膜移植物的存活率。结果在骨髓移植后第14、28、56天，SEB预处理诱导的造血嵌合体水平均高于CYP或NS治疗前。SEB-BMT组的平均角膜移植存活时间(20.3±7.6天)明显长于CYP-BMT组(13.0±4.0天)和NS-BMT组(9.0±2.2天)。与CYP-BMT或NS-BMT小鼠相比，SEB-BMT小鼠脾细胞的MLR反应减弱。SEB-BMT组小鼠外周血和脾组织中的CD4+和CD8+T细胞显著减少。结论SEB预处理后的BMT可促进混合嵌合体的形成，从而抑制同种异体角膜移植排斥反应。这可能与CD4+和CD8+T细胞缺失和获得供者特异性免疫抑制有关。
Purpose We assessed the combined use of Staphylococcal Enterotoxin B (SEB) superantigen pre-treatment along with allogeneic bone marrow transplant (BMT) to induce immune suppression condition and inhibit corneal keratoplasty rejection in mice. Methods BALB/C (H-2d) mice were both BMT and corneal allografts donors and C57BL/6(H-2b) mice were recipients. Prior to BMT, recipients received single injections of either SEB, cyclophosphamide (CYP), or normal saline (NS). Allogenic corneal penetrating keratoplasty was performed 7 days after BMT. Bone marrow chimerisms in recipients (donor major histocompatibility complex-II H2-d) were determined on Days 14, 28, and 56 post-BMT. Recipient immune response was assessed by mixed lymphocyte reactions (MLR) using splenocytes from C57BL/6 mice as responders in co-culture with stimulator cells from C57BL/6 (isogeneic), BALB/C (allogeneic), or CBA/1(third party) mice. Cluster of differentiation 4 receptors positive (CD4+) and CD8+T cells in recipient mice were evaluated. Corneal graft survival was assessed using Kaplan–Meier survival curves. Results SEB pre-treatment induced higher levels of hematopoietic chimerism on Days 14, 28 and 56 post-BMT than did CYP or NS pre-treatment. Mean corneal allograft survival was significantly prolonged with group SEB-BMT (20.3±7.6 days) compared to group CYP-BMT (13.0±4.0 days) and NS-BMT (9.0±2.2 days). SEB-BMT mice splenocytes had diminished MLR responses compared to CYP-BMT or NS-BMT mice. CD4+ and CD8+ T cells in peripheral blood and spleens were significantly reduced in group SEB-BMT mice. Conclusions BMT after SEB pre-treatment could promote mixed chimerism, which inhibited allogeneic cornea transplant rejection. This should possibly relate to CD4+ and CD8+ T cell deletion and acquiring donor-specific immunosuppression.
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影响因子：
4.4
作者：
A. Monaco;M. Wood;J. Gray;P. Russell
通讯作者：
A. Monaco;M. Wood;J. Gray;P. Russell
DOI：
10.1053/bbmt.2001.v7.pm11787527
发表时间：
2001-01-01
影响因子：
4.3
作者：
Mapara, MY;Pelot, M;Sykes, M
通讯作者：
Sykes, M
影响因子：
--
作者：
R. E. Smith;H. McDonald;A. Nesburn;D. Minckler
通讯作者：
R. E. Smith;H. McDonald;A. Nesburn;D. Minckler
DOI：
10.1164/ajrccm.159.1.9712041
发表时间：
1999
影响因子：
24.7
作者：
Si.M Pham;Surindra N. Mitruka;W. Youm;Sen Li;N. Kawaharada;S. Yousem;Y. Colson;S. Ildstad
通讯作者：
Si.M Pham;Surindra N. Mitruka;W. Youm;Sen Li;N. Kawaharada;S. Yousem;Y. Colson;S. Ildstad
由非致死性准备方案诱导的混合嵌合和永久特异性移植耐受。
影响因子：
15.3
作者：
Sharabi, Y;Sachs, D H
通讯作者：
Sachs, D H