DOSE-RELATED MECHANISMS OF IMMUNOSUPPRESSION MEDIATED BY MURINE ANTI-CD3 MONOCLONAL-ANTIBODY IN PANCREATIC-ISLET CELL TRANSPLANTATION AND DELAYED-TYPE HYPERSENSITIVITY

被引:16
作者
MACKIE, JD
PANKEWYCZ, OG
BASTOS, MG
KELLEY, VE
STROM, TB
机构
[1] BRIGHAM & WOMENS HOSP,IMMUNOGENET & TRANSPLANTAT LAB,BOSTON,MA 02115
[2] HARVARD UNIV,CTR STUDY KIDNEY DIS,CAMBRIDGE,MA 02138
关键词
D O I
10.1097/00007890-199006000-00024
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although anti-CD3 mAb therapy is used extensively in clinical transplantation, the dose-related effects and mechanisms of action are not clearly defined. We have examined the dose-related effects of an antimurine CD3 mAb, 145-2C11, in pancreatic islet cell allograft and the delayed type hypersensitivity reaction models of T- cell-dependent immunity. Low-dose anti-CD3 therapy (0.5 μg/day) administered over several days mediated superficially equal, effective clinical immunosuppression as a single high-dose intravenous injection (400 µg). T cells harvested from animals treated with high-dose anti-CD3 were unresponsive to in vitro restimulation. In contrast, T cells isolated from low-dose treated animals retained in vitro proliferative capacity when restimulated with polyvalent anti-CD3 mAb. The terminal complement components were not required to support in vivo immunosuppression mediated by anti-CD3 mAb as C5 deficient mice were immunosuppressed by the administration of this mAb. In some pancreatic islet cell allograft recipients, permanent engraftment, but not tolerance, was achieved. Replacement of donor leukocytes produced acute rejection in hosts bearing longterm, well-accepted grafts. Prolonged anti-CD3 mAb treatment may provide sufficient time for replacement or inactivation of donor leukocytes. © 1990 by Williams & Wilkins.
引用
收藏
页码:1150 / 1154
页数:5
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