T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats.
T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats.
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DOI：
10.4049/jimmunol.156.2.794
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发表时间：
1996-01
影响因子：
4.4
通讯作者：
M. Breban;J. Fernández-Sueiro;J. Richardson;R. R. Hadavand-R.;S. Maika;R. Hammer;J. Taurog
中科院分区：
文献类型：
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作者：
M. Breban;J. Fernández-Sueiro;J. Richardson;R. R. Hadavand-R.;S. Maika;R. Hammer;J. Taurog
人类 MHC I 类基因 HLA-B27 转基因大鼠易患类似于人类 B27 相关疾病的自发性多系统炎症性疾病。这种疾病需要B27转基因产物在造血来源细胞中高水平表达，并且可以通过移植骨髓(BM)或胎肝(FL)细胞过继转移至B27转基因或非转基因大鼠。为了研究 T 细胞和胸腺在疾病过程中所发挥的作用，我们产生了先天性无胸腺 rnu/rnu F344 大鼠，其携带 33-3 系的易患疾病的 B27 转基因位点。转基因裸鼠免受疾病表现。这种保护作用因用 33-3 系正常供体的 T 细胞重建而减弱，其中 CD4 T 细胞在转移疾病方面比 CD8 T 细胞更有效。经致命辐射、成人胸腺切除（ATX）、用来自同系疾病易感品系的完整BM、T细胞耗尽的BM、FL或裸BM重建的非转基因受体均发生疾病。对 ATX 非转基因受体进行预处理以消耗 T 细胞会增强随后转移的疾病。因此，B27 转基因大鼠的炎症性疾病是 T 细胞依赖性的。相关T细胞不需要在胸腺中遇到B27，残留的抗辐射和/或胸腺外来源的宿主T细胞足以介导过继转移的疾病。这些数据与 B27 介导的疾病模型最为一致，该疾病是由于耐受失败并需要 CD4 T 细胞群而引起的。
Rats transgenic for the human MHC class I gene HLA-B27 are susceptible to a spontaneous multisystem inflammatory disease that resembles human B27-associated disease. This disease requires a high level of expression of the B27 transgene product in cells of hemopoietic origin and can be adoptively transferred to B27 transgenic or nontransgenic rats by transplantation of bone marrow (BM) or fetal liver (FL) cells. To investigate the role played by T cells and the thymus in the disease process, we produced congenitally athymic rnu/rnu F344 rats carrying the disease-prone B27 transgenic locus of the 33-3 line. Transgenic nude rats were protected from disease manifestations. This protection was abated by reconstitution with T cells from euthymic donors of the 33-3 line, with CD4 T cells being more efficient than CD8 T cells in transferring disease. Lethally irradiated, adult-thymectomized (ATX), nontransgenic recipients reconstituted with intact BM, T cell-depleted BM, FL, or nude BM from syngeneic disease-prone lines all developed disease. Pretreatment of the ATX nontransgenic recipients to deplete T cells enhanced the subsequent transferred disease. The inflammatory disease of B27 transgenic rats is thus T cell-dependent. The relevant T cells do not need to encounter B27 in the thymus, and residual radioresistant and/or extrathymically derived host T cells are sufficient to mediate the adoptively transferred disease. The data are most consistent with a model of B27-mediated disease arising from a failure of tolerance and requiring a population of CD4 T cells.