Nakagawa T, Nagata N, Hosaka N, Inaba M, Yasumizu R, Ogawa R, Ikehara S
1st Department of Pathology, Kansai Medical University, Osaka, Japan.
Cell Immunol. 1991 Oct 1;137(1):189-99. doi: 10.1016/0008-8749(91)90068-m.
When MRL/Mp(-)+/+(MRL/+) mice are lethally irradiated and then reconstituted with MRL/Mp-lpr/lpr (MRL/lpr) bone marrow and/or spleen cells, these MRL/+ mice develop "lpr-GVHD" which is similar to acute graft-versus-host disease (GVHD). Using a Thy-1 congenic strain of MRL/lpr mice (MRL/lpr-Thy-1.1), we analyzed T cell subpopulations in the thymus and spleen of MRL/+ mice suffering from lpr-GVHD. lpr-GVHD was induced in MRL/+ mice by transplantation of bone marrow cells (BMC) from MRL/lpr-Thy-1.1 mice; severe lymphocyte depletion associated with fibrosis was observed in the spleens after 7 weeks of bone marrow transplantation (BMT). Thymocytes of the host MRL/+ thymus were replaced with donor-derived cells from the early stage of lpr-GVHD, whereas in the spleen, a small number of host T cells (Thy-1.2+) (4-5%) were retained until the late stage of lpr-GVHD. Donor-type (Thy-1.1+) T cell subsets were not different from those of nontreated MRL/+ mice in the thymus, whereas in the spleen. CD8+ T cells (Thy-1.1+) reached a peak at 5 weeks after BMT, and CD4+ T cells (Thy-1.1+), a peak at 6 weeks. The elimination of T cells from MRL/lpr BMC had no evident effect on the prevention of lpr-GVHD. T cell subpopulations showed a similar pattern to GVHD elicited by MHC differences. Analyses of autoreactive T cells expressing V beta 5 or V beta 11 revealed that autoreactive T cells were deleted from the peripheral lymph nodes. Interestingly, the levels of IgG anti-ssDNA antibodies markedly increased, and both IgM and IgG rheumatoid factors slightly increased 5 to 7 weeks after BMT. These findings are discussed in relation to not only GVHD elicited by MHC differences but also autoimmune diseases.
当对MRL/Mp(-)+/+(MRL/+)小鼠进行致死性照射，然后用MRL/Mp-lpr/lpr（MRL/lpr）骨髓和/或脾细胞进行重建时，这些MRL/+小鼠会发生“lpr移植物抗宿主病”（lpr-GVHD），这与急性移植物抗宿主病（GVHD）相似。使用MRL/lpr小鼠的Thy-1同基因品系（MRL/lpr-Thy-1.1），我们分析了患有lpr-GVHD的MRL/+小鼠胸腺和脾脏中的T细胞亚群。通过移植来自MRL/lpr-Thy-1.1小鼠的骨髓细胞（BMC）在MRL/+小鼠中诱导lpr-GVHD；骨髓移植（BMT）7周后，在脾脏中观察到与纤维化相关的严重淋巴细胞耗竭。宿主MRL/+胸腺的胸腺细胞在lpr-GVHD早期就被供体来源的细胞所取代，而在脾脏中，少量宿主T细胞（Thy-1.2+）（4-5%）一直保留到lpr-GVHD晚期。在胸腺中，供体型（Thy-1.1+）T细胞亚群与未处理的MRL/+小鼠的T细胞亚群没有差异，而在脾脏中，CD8+T细胞（Thy-1.1+）在BMT后5周达到峰值，CD4+T细胞（Thy-1.1+）在6周达到峰值。从MRL/lpr BMC中去除T细胞对预防lpr-GVHD没有明显效果。T细胞亚群显示出与由MHC差异引发的GVHD相似的模式。对表达Vβ5或Vβ11的自身反应性T细胞的分析表明，自身反应性T细胞从外周淋巴结中被清除。有趣的是，IgG抗单链DNA抗体水平显著升高，并且在BMT后5至7周，IgM和IgG类风湿因子均略有升高。这些发现不仅与由MHC差异引发的GVHD有关，还与自身免疫性疾病有关进行了讨论。
