Hölscher C, Hasch G, Joswig N, Stauffer U, Müller U, Mossmann H
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Vet Immunol Immunopathol. 1999 Sep 1;70(1-2):67-83. doi: 10.1016/s0165-2427(99)00065-3.
The long term immune responsiveness of bovine peripheral blood lymphocytes engrafted into severe combined immunodeficient mice (bovine PBL SCID mice) was analyzed. After intraperitoneal transfer (i.p.) of 2x10(7) bovine PBL into SCID mice, FACS analysis revealed successful engraftment of bovine CD4 and CD8+ T cells in the peritoneal cavity, the peripheral blood, spleen, lymph nodes, bone marrow, and thymus of reconstituted mice for up to 13 weeks. As shown by immunocytochemistry in sections of spleens from SCID mice 16 weeks after substitution, bovine T and B cells were localized perivasculary forming pseudofollicular structures. Nevertheless, histopathology of spleen and liver from bovine PBL SCID mice revealed pathological alterations indicating rejection of xenogenic cells or graft versus host disease (GVHD). On the functional level, i.p. transfer of bovine PBL into SCID mice induced increasing levels of bovine IgM and IgG in the sera of recipients. Bovine Ig could be detected up to 20 weeks. Immunization of SCID mice reconstituted with PBL of normal donors with dinitrophenol (DNP)-edestin induced a weak specific bovine antibody response in recipient mice. In contrast, a secondary specific bovine IgG response was observed after antigen restimulation of SCID mice reconstituted with PBL from calves preimmunized either with DNP-edestin or keyhole limpet hemocyanin (KLH) showing functional T cell-independent and -dependent antibody responses of bovine PBL SCID mice. Our data demonstrate that transfer of bovine PBL into SCID mice leads to a long term engraftment of bovine cells in lymphatic and non-lymphatic organs inducing a functional substitution of T and B cell immune response of SCID mice. Therefore, bovine PBL SCID chimera can serve as a small animal model for the analysis of bovine lymphopoiesis and infectious diseases of cattle.
分析了移植到严重联合免疫缺陷小鼠（牛外周血淋巴细胞-严重联合免疫缺陷小鼠）体内的牛外周血淋巴细胞的长期免疫反应性。将2×10⁷个牛外周血淋巴细胞经腹腔注射（i.p.）到严重联合免疫缺陷小鼠体内后，流式细胞术分析显示，在长达13周的时间里，牛CD4和CD8⁺T细胞成功植入重构小鼠的腹腔、外周血、脾脏、淋巴结、骨髓和胸腺。如替代16周后严重联合免疫缺陷小鼠脾脏切片的免疫细胞化学所示，牛T细胞和B细胞位于血管周围，形成假滤泡结构。然而，牛外周血淋巴细胞-严重联合免疫缺陷小鼠的脾脏和肝脏组织病理学显示出病理改变，表明存在异种细胞排斥或移植物抗宿主病（GVHD）。在功能水平上，将牛外周血淋巴细胞经腹腔注射到严重联合免疫缺陷小鼠体内可诱导受体血清中牛IgM和IgG水平升高。牛Ig可持续检测到20周。用二硝基苯酚（DNP）-麻籽球蛋白免疫由正常供体的外周血淋巴细胞重构的严重联合免疫缺陷小鼠，在受体小鼠中诱导出较弱的特异性牛抗体反应。相比之下，在用DNP-麻籽球蛋白或钥孔戚血蓝蛋白（KLH）预免疫的小牛的外周血淋巴细胞重构的严重联合免疫缺陷小鼠经抗原再刺激后，观察到二次特异性牛IgG反应，显示出牛外周血淋巴细胞-严重联合免疫缺陷小鼠的功能性T细胞非依赖性和依赖性抗体反应。我们的数据表明，将牛外周血淋巴细胞移植到严重联合免疫缺陷小鼠体内可导致牛细胞在淋巴和非淋巴器官中长期植入，诱导严重联合免疫缺陷小鼠的T细胞和B细胞免疫反应发生功能性替代。因此，牛外周血淋巴细胞-严重联合免疫缺陷嵌合体可作为一种小动物模型，用于分析牛的淋巴细胞生成和牛的传染病。
