Youssef Abdel-Rahman, Otley Carolyn, Mathieson Peter W, Smith Richard M
Academic Renal Unit, Southmead Hospital, University of Bristol, Bristol BS10 5NB, UK.
Transpl Int. 2002 Jun;15(6):302-9. doi: 10.1007/s00147-002-0407-z. Epub 2002 Apr 20.
Cytotoxic T lymphocytes (CTLs) and macrophage-mediated delayed-type hypersensitivity (DTH) responses may both mediate allograft rejection. Furthermore, although allograft rejection is classically considered a type [22, 23, 38, 50, 52] 1 cellular immune response, type-2 cytokines can support rejection. This study examines whether the immunogenicity of the transplanted tissue, as determined by type of tissue (skin versus heart) and degree of antigenic mismatch, influences recruitment of these effector mechanisms. Graft survival, histological appearance and intragraft gene expression (IL-2, IFN-gamma, IL-12 p40, IL-4, IL-10, perforin, Fas ligand (Fas L), iNOS and TNF-alpha) were compared for fully allogeneic, minor histocompatibility (mHC) antigen-mismatched and syngeneic skin and heart grafts. We found mRNA characteristic of CTLs and DTH responses in fully allogeneic and mHC antigen-mismatched skin and heart grafts. Concomitant type-1 and type-2 cytokine gene transcription was seen. These findings demonstrate that the tissue grafted and degree of antigenic disparity between donor and recipient do not restrict the repertoire of cellular immune responses involved in graft rejection. This finding has implications in the design of new immunosuppressive strategies for clinical transplantation.
细胞毒性T淋巴细胞（CTLs）和巨噬细胞介导的迟发型超敏反应（DTH）都可能介导同种异体移植排斥反应。此外，尽管经典地认为同种异体移植排斥反应是一种1型细胞免疫反应，但2型细胞因子也可支持排斥反应。本研究探讨移植组织的免疫原性（由组织类型（皮肤与心脏）和抗原错配程度决定）是否会影响这些效应机制的募集。比较了完全同种异体、次要组织相容性（mHC）抗原错配和同基因皮肤及心脏移植物的移植物存活、组织学外观和移植物内基因表达（IL-2、IFN-γ、IL-12 p40、IL-4、IL-10、穿孔素、Fas配体（Fas L）、诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子-α（TNF-α））。我们在完全同种异体和mHC抗原错配的皮肤及心脏移植物中发现了CTLs和DTH反应的mRNA特征。同时观察到1型和2型细胞因子基因转录。这些发现表明，移植的组织以及供体与受体之间的抗原差异程度并不限制参与移植排斥反应的细胞免疫反应谱。这一发现对临床移植新免疫抑制策略的设计具有重要意义。
