Breban M, Hammer R E, Richardson J A, Taurog J D
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
J Exp Med. 1993 Nov 1;178(5):1607-16. doi: 10.1084/jem.178.5.1607.
We have previously produced lines of rats transgenic for HLA-B27 and human beta 2-microglobulin (h beta 2m) that develop a progressive inflammatory disease sharing many clinical and histologic features with the B27-associated human spondyloarthropathies, including gut and male genital inflammation, arthritis, and psoriasiform skin lesions. Other transgenic lines that express lower levels of B27 and h beta 2m remain healthy. To investigate the cellular basis for the multisystem inflammatory disease in these rats, we transferred lymphoid cell populations from disease-prone transgenic lines to irradiated disease-resistant transgenic and nontransgenic recipients. In recipients of cells from two different disease-prone lines, successful transfer required engraftment of bone marrow cells. Transfer of disease with fetal liver cells suggested that neither mature effector cells nor active disease in the donors was necessary for induction of disease in the recipients. Remission of the spontaneous disease in irradiated transgenic rats was induced by engraftment of nontransgenic bone marrow. These results suggest that the expression of HLA-B27 in bone marrow-derived cells alone is sufficient for the development of B27-associated disease, and that disease transfer requires engraftment of a bone marrow precursor cell for which mature cells in spleen or in lymph node cannot substitute.
我们之前培育出了携带HLA - B27和人β2 - 微球蛋白（hβ2m）的转基因大鼠品系，这些大鼠会患上一种进行性炎症性疾病，该疾病与B27相关的人类脊柱关节病具有许多临床和组织学特征，包括肠道和男性生殖器炎症、关节炎以及银屑病样皮肤病变。其他表达较低水平B27和hβ2m的转基因品系则保持健康。为了研究这些大鼠多系统炎症性疾病的细胞基础，我们将易患疾病的转基因品系的淋巴细胞群体转移到经辐照的抗病转基因和非转基因受体中。在来自两个不同易患疾病品系的细胞受体中，成功转移需要骨髓细胞的植入。用胎肝细胞转移疾病表明，供体中的成熟效应细胞或活动性疾病对于受体中疾病的诱导都不是必需的。经辐照的转基因大鼠的自发性疾病通过植入非转基因骨髓得以缓解。这些结果表明，仅骨髓来源细胞中HLA - B27的表达就足以引发B27相关疾病，并且疾病转移需要植入一种骨髓前体细胞，而脾脏或淋巴结中的成熟细胞无法替代该前体细胞。
