CD2 antigen targeting reduces intragraft expression of mRNA-encoding granzyme B and IL-10 and induces tolerance

被引:16
作者
Kapur, S
Khanna, A
Sharma, VK
Li, BG
Suthanthiran, M
机构
[1] CORNELL UNIV, MED CTR, NEW YORK HOSP, DIV NEPHROL, ROGOSIN INST, NEW YORK, NY 10021 USA
[2] CORNELL UNIV, MED CTR,NEW YORK HOSP,DIV NEPHROL,ROGOSIN INST, DEPT MED, NEW YORK, NY 10021 USA
[3] CORNELL UNIV, MED CTR,NEW YORK HOSP,DIV NEPHROL,ROGOSIN INST, DEPT SURG, NEW YORK, NY 10021 USA
[4] CORNELL UNIV, MED CTR,NEW YORK HOSP,DIV NEPHROL,ROGOSIN INST, DEPT BIOCHEM, NEW YORK, NY 10021 USA
关键词
D O I
10.1097/00007890-199607270-00017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We explored the hypothesis that CD2 antigen-specific therapy would reduce intragraft gene expression and facilitate the emergence of transplantation tolerance. This postulate was tested in a murine pancreatic islet cell allograft model in which a novel mAb directed at the CD2 antigen, RM2-2 anti-CD2 mAb (RM2-2 mAb), was used to regulate CD2 antigen-dependent antiallograft response. Peritransplant administration (day -1, 0, and day +1 with respect to transplantation) of RM2-2 mAb resulted in significantly longer survival of DBA/2 pancreatic islet cell allografts in the B6AF1 recipient compared with untreated recipients, RM2-2 mAb therapy facilitated the induction of antigen-specific tolerance: whereas retransplantation with the original donor strain (DBA/2) islet cell allograft was successful, retransplantation with a third-party donor (SJL) islet cell allograft was not. In vivo administration of RM2-2 mAb therapy resulted in a decrease in the percentage of T cells that coexpressed the CD2 antigen (demonstrated by two-color flow cytometry) and in a decrease in intragraft expression of cytotoxic cell specific granzyme B mRNA and IL-10 mRNA (detected by RT-PCR). Our data, in addition to demonstrating for the first time the efficacy of RM2-2 anti-CD2 mAb, suggest that CD2 antigen is a suitable target for the induction of transplantation tolerance.
引用
收藏
页码:249 / 255
页数:7
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