Ikarashi Y, Abo T, Kawai K, IIai T, Watanabe H, Suzuki K, Matsumoto Y, Omata S, Fujiwara M
Department of Biosystem Science, Graduate School of Science and Technology, Niigata University, Japan.
Immunology. 1994 Oct;83(2):205-12.
Chronic graft-versus-host disease (GVHD) following bone marrow transplantation often gives rise to a severe autoimmune-like state. To investigate the immunopathogenesis of this diseased state, mice receiving a transplant of lymphocytes with major histocompatibility complex (MHC) class II disparity (the simplest model of chronic GVHD) were examined. (B10.Thy-1.1 x B6.C-H-2bm12) F1 mice were injected with parental B10.Thy-1.1 CD4+ splenic T cells. These mice showed intensive lymphocyte infiltration of the target organs, including the liver, salivary glands and pancreas. Indeed, the cell numbers yielded from the spleen and liver were increased, and polyclonal B-cell activation was induced by 14 days after injection. More strikingly, more than 80% of such expanding lymphocytes in the target organs became T cells with T-cell receptors (TCR) of intermediate intensity (i.e. intermediate TCR cells) that carried the properties of extrathymic origin. Despite the homogeneous expansion of intermediate TCR cells in GVHD mice, these T cells were polyclonal in terms of V beta usage. These results, in conjunction with the data using the thymectomized mice as recipients, suggested that extrathymic, intermediate TCR cells possibly of recipient origin might be intimately related to the pathogenesis of the autoimmune-like state resulting from chronic GVHD.
骨髓移植后的慢性移植物抗宿主病（GVHD）常常引发一种严重的自身免疫样状态。为了研究这种疾病状态的免疫发病机制，对接受具有主要组织相容性复合体（MHC）II类差异的淋巴细胞移植的小鼠（慢性GVHD的最简单模型）进行了检查。给（B10.Thy-1.1×B6.C-H-2bm12）F1小鼠注射亲代B10.Thy-1.1 CD4 +脾T细胞。这些小鼠的靶器官，包括肝脏、唾液腺和胰腺，出现了密集的淋巴细胞浸润。实际上，注射后14天脾脏和肝脏中的细胞数量增加，并且诱导了多克隆B细胞活化。更引人注目的是，靶器官中超过80%的此类扩增淋巴细胞变成了具有中等强度T细胞受体（TCR）的T细胞（即中等TCR细胞），这些细胞具有胸腺外起源的特性。尽管GVHD小鼠中中等TCR细胞均匀扩增，但这些T细胞在Vβ使用方面是多克隆的。这些结果，结合使用胸腺切除小鼠作为受体的数据，表明胸腺外的、可能源自受体的中等TCR细胞可能与慢性GVHD导致的自身免疫样状态的发病机制密切相关。
