Madariaga Maria Lucia L, Michel Sebastian G, La Muraglia Glenn M, Sihag Smita, Leonard David A, Farkash Evan A, Colvin Robert B, Cetrulo Curtis L, Huang Christene A, Sachs David H, Madsen Joren C, Allan James S
Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, MA.
Transplantation. 2015 Jul;99(7):1372-8. doi: 10.1097/TP.0000000000000676.
Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by passenger leukocytes in the rejection or acceptance of an organ is unclear. We tested whether recipient-matching of donor graft passenger leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation.
In the experimental group (group 1), donor lungs were obtained from chimeric swine, in which the passenger leukocytes (but not the parenchyma) were major histocompatibility complex-matched to the recipients (n = 3). In the control group (group 2), both the donor parenchyma and the passenger leukocytes were major histocompatibility complex-mismatched to the recipients (n = 3).
Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of passenger leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing passenger leukocytes matched to the lung recipient (group 1) survived on average 107 days (range, 80-156). Control lung allografts (group 2) survived on average 45 days (range, 29-64; P < 0.05).
Our data indicate that recipient-matching of passenger leukocytes significantly prolongs lung allograft survival.
同种异体移植排斥仍是临床肺移植中一个棘手的问题,过客白细胞在器官排斥或接受过程中所起的作用尚不清楚。我们在原位左肺移植的临床前模型中测试了供体移植物过客白细胞与受体匹配是否会影响移植物存活。
在实验组(第1组)中,供体肺取自嵌合猪,其中过客白细胞(而非实质组织)与受体的主要组织相容性复合体相匹配(n = 3)。在对照组(第2组)中,供体实质组织和过客白细胞均与受体的主要组织相容性复合体不匹配(n = 3)。
通过免疫组织化学和流式细胞术检测,使用受体型细胞进行造血干细胞移植预先构建为嵌合体的猪所提供的肺显示出高度的过客白细胞嵌合现象。含有与肺受体匹配的过客白细胞的嵌合肺(第1组)平均存活107天(范围80 - 156天)。对照肺同种异体移植物(第2组)平均存活45天(范围29 - 64天;P < 0.05)。
我们的数据表明,过客白细胞与受体匹配可显著延长肺同种异体移植物的存活时间。