Role of intrathymic rat class II+ cells in maintaining deletional tolerance in xenogeneic rat→mouse bone marrow chimeras
Role of intrathymic rat class II+ cells in maintaining deletional tolerance in xenogeneic rat→mouse bone marrow chimeras
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DOI：
10.1097/00007890-199805150-00013
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发表时间：
1998-05-15
期刊：
影响因子：
6.2
通讯作者：
Sykes, M
中科院分区：
文献类型：
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作者：
Nikolic, B;Lei, H;Sykes, M
背景：在非清髓性方案处理的小鼠中，随后注射T细胞去除的大鼠骨髓细胞，可以诱导混合异种骨髓嵌合体和耐受。我们假设，尽管在这些嵌合体中观察到大鼠造血功能逐渐下降，但只要大鼠II类+抗原呈递细胞保留在其胸腺中，由于供体反应性胸腺细胞的缺失，耐受性将持续存在。随着时间的推移，对嵌合体水平以及小鼠V β 5和V β 11 T细胞缺失的水平进行跟踪。这些结果与免疫组化法检测的大鼠胸腺中II类+细胞的存在以及体内和体外试验检测的长期嵌合体中耐受性的存在相关。(1)增殖和细胞毒性测定以及皮肤移植物存活证明存在对宿主和供体大鼠的特异性耐受性，对第三方大鼠和小鼠刺激物具有正常反应性，甚至迟至骨髓移植后85周，（2）胸腺和外周中缺乏成熟的V β 5（+）和V β 11（+）宿主T细胞总是与胸腺中存在大鼠II类+细胞有关，并且在大鼠胸腺中观察到表达这些V β家族的T细胞的不完全缺失，其中未检测到II+类细胞。供体特异性T细胞耐受性在供体型重建下降期间维持，并且最有可能通过识别II类+大鼠细胞上表达的抗原的T细胞的胸腺内克隆缺失介导。
Background, Mixed xenogeneic bone marrow chimerism and tolerance can be induced in mice conditioned with a nonmyeloablative regimen followed by injection of T cell-depleted rat bone marrow cells. We hypothesized that, despite a gradual decline in rat hematopoiesis observed in these chimeras, as long as rat class II+ antigen-presenting cells remain in their thymi, tolerance will persist as a result of deletion of donor-reactive thymocytes.Methods. The level of chimerism and of mouse V beta 5 and V beta 11 T-cell deletion was followed over time. These results were correlated with the presence of rat class II+ cells in the thymus by immunohistochemistry and the presence of tolerance in long-term chimeras by in vivo and in vitro assays.Results. (1) Proliferation and cytotoxicity assays, as well as skin graft survival, demonstrated the presence of specific tolerance to host and to donor rat, with normal reactivity to third-party rat and mouse stimulators, even as late as 85 weeks after bone marrow transplantation, (2) The absence of mature V beta 5(+) and V beta 11(+) host T cells in the thymus and periphery was always associated with the presence of rat class II+ cells in the thymus, and incomplete deletion of T cells expressing these V beta families was observed in thymi in which rat class II+ cells were not detectable.Conclusions. Donor-specific T-cell tolerance is maintained during the period when donor-type reconstitution declines, and is most likely mediated by intrathymic clonal deletion of T cells that recognize antigens expressed on class II+ rat cells.