Kelly K E, Hertz M I, Mueller D L
Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Transplantation. 1998 Sep 27;66(6):764-71. doi: 10.1097/00007890-199809270-00011.
One third of human lung allografts develop chronic rejection manifested as obliterative bronchiolitis. Heterotopically transplanted allogeneic murine tracheas develop obliterative airway disease (OAD) leading to a lesion resembling human obliterative bronchiolitis. The purpose of this study was to determine the T-cell and major histocompatibility complex (MHC) molecule requirements of murine OAD.
BALB/c allografts and C57BL/6 (B6) isografts were transplanted into B6 severe combined immunodeficient (SCID) and B6 wild-type (WT) recipients. MHC class I-discrepant bm1 grafts, class II-discrepant bm12 grafts, and F1(bm1 x bm12) (F1) grafts also were transplanted into B6 WT recipients. Grafts were harvested between days 5 and 56 following transplantation and evaluated histologically.
Complete MHC-disparate allografts placed in WT recipients had significantly more disease than similar allografts in SCID recipients, and the latter were indistinguishable from isografts in either WT or SCID recipients, indicating a lymphocyte dependence on the disease development. Pathology was significantly more severe in bm1 and F1 allografts than in isografts recovered from B6 recipients, but bm12 allografts appeared no different than isografts. T-cell infiltrates in these bm12 allografts contained only CD4+ cells, whereas infiltrates in the BALB/c, bm1, and F1 allografts manifesting OAD contained both CD4+ and CD8+ cells. No grafts had significant B-cell infiltration.
These findings suggest that OAD relies on a host T-cell response that includes CD8+ cells, directed against allo-class I-bearing donor cells within the graft.
三分之一的人肺移植会发生慢性排斥反应，表现为闭塞性细支气管炎。异体小鼠气管异位移植会发生闭塞性气道疾病（OAD），导致出现类似于人类闭塞性细支气管炎的病变。本研究的目的是确定小鼠OAD的T细胞和主要组织相容性复合体（MHC）分子需求。
将BALB/c同种异体移植物和C57BL/6（B6）同基因移植物移植到B6重度联合免疫缺陷（SCID）和B6野生型（WT）受体中。MHC I类不匹配的bm1移植物、II类不匹配的bm12移植物和F1（bm1×bm12）（F1）移植物也被移植到B6 WT受体中。在移植后第5天至第56天之间采集移植物，并进行组织学评估。
置于WT受体中的完全MHC不匹配的同种异体移植物比置于SCID受体中的类似同种异体移植物有明显更多的疾病，并且后者与WT或SCID受体中的同基因移植物没有区别，表明淋巴细胞对疾病发展有依赖性。bm1和F1同种异体移植物的病理学比从B6受体中回收的同基因移植物严重得多，但bm12同种异体移植物看起来与同基因移植物没有差异。这些bm12同种异体移植物中的T细胞浸润仅包含CD4+细胞，而表现出OAD的BALB/c、bm1和F1同种异体移植物中的浸润包含CD4+和CD8+细胞。没有移植物有明显的B细胞浸润。
这些发现表明，OAD依赖于宿主T细胞反应，其中包括CD8+细胞，针对移植物内携带同种异体I类的供体细胞。
