Fractionated dosing of cyclophosphamide for establishing long-lasting skin allograft survival, stable mixed chimerism, and intrathymic clonal deletion in mice primed with allogeneic spleen cells.
Fractionated dosing of cyclophosphamide for establishing long-lasting skin allograft survival, stable mixed chimerism, and intrathymic clonal deletion in mice primed with allogeneic spleen cells.
复制标题
环磷酰胺的分级剂量用于在用同种异体脾细胞引发的小鼠中建立持久的同种异体皮肤移植存活、稳定的混合嵌合状态和胸腺内克隆缺失。
DOI：
10.1097/00007890-199706150-00022
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
H. Yasui
中科院分区：
文献类型：
--
作者：
Q. Zhang;H. Mayumi;M. Umesue;Y. Tomita;K. Nomoto;H. Yasui
背景
BACKGROUND
Injection of allo-spleen cells (SC) followed by a single dose of cyclophosphamide (CP) can induce tolerance of tumor and/or skin allografts in mice. To minimize the damage caused by CP, fractionation of CP that can establish long-lasting skin graft survival, stable mixed chimerism, and intrathymic clonal deletion in the host was investigated in the present study.
METHODS
Allo-SC (10(8)) were given intravenously on day 0. CP at 200 mg/kg was given intraperitoneally on day 2 in a single dose (CP 200x1 group). CP at 100, 66, 50, 40, and 33 mg/kg was given daily from day 1 through days 2, 3, 4, 5 and 6, respectively, in the fractionated doses (CP 100x2, 66x3, 50x4, 40x5, and 33x6 groups; total dose=200 mg/kg). Allografting was performed on day 14.
RESULTS
In a fully allogeneic combination of C57BL/6 (H2b)-->AKR (H2k, Mls-1a), an EL-4 tumor (H2b) was specifically accepted to kill the AKR mice in all of the SC+CP 200x1, 100x2, 66x3, 50x4, 40x5, and 33x6 groups (n=6), but C57BL/6 skin graft survival was not prolonged in any of the tumor-tolerant groups. In an H2-identical combination of AKR-->C3H (H2k, Mls-1b), AKR skin graft survival was prolonged remarkably (80-90 days) in the SC+CP 200x1, 100x2, and 66x3 groups (n=5-11), but was prolonged moderately (20-60 days) in the SC+CP 50x4 and 40x5 groups. In both of the SC+CP 200x1 and 66x3 groups in the AKR-->C3H combination, mixed chimerism was maintained for as long as 100 days after tolerance induction in both the spleen and thymus, associated with intrathymic clonal deletion of Vbeta6+ T cells. The decreases in leukocyte count, hemoglobin level, spleen weight, SC count, and body weight were significantly smaller in the SC+CP 66x3 group than in the SC+CP 200x1 group.
CONCLUSIONS
Fractionated CP is effective in ameliorating the compromised state induced by a single dose of CP. To induce a long-lasting skin allograft survival associated with stable mixed chimerism and intrathymic clonal deletion in an H2-identical combination, 200 mg/kg of CP can be divided into three or fewer fractions.
使用两步法和耐受诱导的遗传分析来诱导跨主要障碍的耐受。
影响因子：
2.8
作者：
Mayumi,H;Good,RA
通讯作者：
Good,RA