Murase N, Demetris A J, Woo J, Tanabe M, Furuya T, Todo S, Starzl T E
Pittsburgh Transplant Institute, University of Pittsburgh Health Science Center, Pennsylvania 15213.
Transplantation. 1993 Jan;55(1):1-7. doi: 10.1097/00007890-199301000-00001.
In LEW rats treated daily with variable doses of FK506 for 14 days and weekly thereafter, successful intestinal transplantation from fully allogeneic BN donors never was complicated by fatal GVHD. In contrast, with LEW-to-BN transplantation, rejection was difficult to control and GVHD developed after the end of the daily treatment. However, FK506 in high daily doses continued after the initial 14-day course could prevent this GVHD or even reverse it after allowing its onset. Further experiments did not clarify why the BN rat was an "easy" donor and "difficult" recipient. In unaltered animals the lymphocyte population of normal LEW rats had a higher proportion of T cells, fewer B cells, and a lower CD4:CD8 ratio than normal BN rats. However, one-way MLR reactions of the BN and LEW combinations were generally similar in either direction and not affected differently by the addition of FK506 to the medium. The two-way lymphocyte traffic from graft to host lymphoid organs and vice versa also was similar with BN-to-LEW and LEW-to-BN models. The BN rat may be a useful tool to investigate inadequately explained mechanisms of GVHD.
在每天用不同剂量的FK506处理14天、之后每周处理一次的LEW大鼠中,来自完全异基因BN供体的成功肠移植从未并发致命的移植物抗宿主病(GVHD)。相比之下,在LEW到BN的移植中,排斥反应难以控制,且在每日治疗结束后发生了GVHD。然而,在最初的14天疗程后继续给予高剂量的每日FK506可以预防这种GVHD,甚至在其发生后使其逆转。进一步的实验并未阐明为什么BN大鼠是“容易的”供体和“困难的”受体。在未改变的动物中,正常LEW大鼠的淋巴细胞群体比正常BN大鼠具有更高比例的T细胞、更少的B细胞以及更低的CD4:CD8比率。然而,BN和LEW组合的单向混合淋巴细胞反应(MLR)在两个方向上通常相似并且不受向培养基中添加FK506的不同影响。在BN到LEW和LEW到BN模型中,从移植物到宿主淋巴器官以及反之亦然的双向淋巴细胞迁移也相似。BN大鼠可能是研究未充分解释的GVHD机制的有用工具。