Malyguine A M, Saadi S, Platt J L, Dawson J R
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Transplantation. 1996 Nov 15;62(9):1319-24. doi: 10.1097/00007890-199611150-00025.
The use of baboons as a model for the study of allo- and xenotransplantation has become increasingly important, but there are few studies on the basic immunological responses in baboons that might be relevant for a rejection reaction. In present study, the cell-surface phenotype, cytokine-induced activation and growth, and cytotoxicity of baboon and human natural killer (NK) and lymphokine-activated killer (LAK) cells were compared. A panel of murine monoclonal antibodies specific for human cell-surface markers expressed on lymphocytes was used to compare relevant baboon and human peripheral blood lymphocytes (PBL). Baboon PBL were 52.1+/-2.9% CD8+, 18.5+/-2.2% CD16+, 3.0+/-0.5% CD25+, and 5.5+/-1.8% CD69+. The corresponding proportions in humans were 23.8+/-7.1%, 12.8+/-3.2%, 4.5+/-1.0%, and 2.3+/-1.1%. In contrast to human PBL, less than 1% of baboon lymphocytes expressed CD56, CD57, and CD122 (interleukin [IL]-2Rbeta). Baboon lymphocytes showed NK cytotoxic activity against the human K562 and CEM cell lines, which was comparable to human NK activity. Depletion of baboon CD16+ or CD8+ cells led to dramatic decreases in NK cytotoxicity, and removal of both subsets completely abrogated NK activity. Incubation of baboon lymphocytes with human recombinant IL-2 for 1 week led to the appearance of CD56+ cells (11.3+/-2.8%). Most of the baboon CD56+ cells induced in culture were in S and G2 phases of cell cycle. Both baboon and human IL-2-activated lymphocytes were highly cytotoxic against the human LAK-sensitive cell line Daudi. Depletion of baboon CD8+ but not CD56+ cells significantly decreased LAK activity. These studies revealed differences in the NK system of humans and baboons that should be taken into consideration when analyzing immune responses to allo- and xenotransplantation in baboons.
将狒狒作为同种异体移植和异种移植研究模型的应用变得越来越重要,但关于狒狒可能与排斥反应相关的基本免疫反应的研究却很少。在本研究中,比较了狒狒和人类自然杀伤(NK)细胞及淋巴因子激活的杀伤(LAK)细胞的细胞表面表型、细胞因子诱导的激活和生长以及细胞毒性。使用一组针对淋巴细胞上表达的人类细胞表面标志物的鼠单克隆抗体来比较相关的狒狒和人类外周血淋巴细胞(PBL)。狒狒PBL中CD8 + 细胞占52.1±2.9%,CD16 + 细胞占18.5±2.2%,CD25 + 细胞占3.0±0.5%,CD69 + 细胞占5.5±1.8%。人类相应的比例分别为23.8±7.1%、12.8±3.2%、4.5±1.0%和2.3±1.1%。与人类PBL不同,不到1%的狒狒淋巴细胞表达CD56、CD57和CD122(白细胞介素[IL]-2Rβ)。狒狒淋巴细胞对人类K562和CEM细胞系表现出NK细胞毒性活性,这与人类NK活性相当。去除狒狒CD16 + 或CD8 + 细胞会导致NK细胞毒性显著降低,而去除这两个亚群则完全消除NK活性。将狒狒淋巴细胞与人重组IL-2孵育1周会导致CD56 + 细胞出现(11.3±2.8%)。培养诱导产生的大多数狒狒CD56 + 细胞处于细胞周期的S期和G2期。狒狒和人类IL-2激活的淋巴细胞对人类LAK敏感细胞系Daudi均具有高度细胞毒性。去除狒狒CD8 + 细胞而非CD56 + 细胞会显著降低LAK活性。这些研究揭示了人类和狒狒NK系统的差异,在分析狒狒对同种异体移植和异种移植的免疫反应时应予以考虑。