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【medical-news】Blood:体外光化学细胞疗法可逆转移

NEW YORK (Reuters Health) Sept 05 - Cells treated with extracorporeal photopheresis (ECP) can reverse graft-versus-host disease (GVHD) by increasing donor regulatory T cells and by indirectly reducing the number of donor effector lymphocytes that have not undergone ECP, according to the findings of a study that used two well-established mouse models.

"This study is an example of reverse translation. Instead of 'bench to bedside,' we have brought a treatment already used in the clinic back to the laboratory to try to gain insight about how it might work," Dr. Erin Gatza of the University of Michigan Cancer Center, Ann Arbor, told Reuters Health.

These findings "underscore the importance of T regulatory cells in the control of GVHD and the ability to induce those cells using ECP. These data might have implications for other T cell-mediated inflammatory diseases in addition to GVHD, including autoimmunity and solid organ rejection."

In ECP, isolated white blood cells are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet-A light, the researchers explain in the August 15 issue of Blood. Although 8-MOP is normally biologically inert, in the presence of UVA light, it cross-links DNA and causes apoptosis. Although ECP is used to treat cutaneous T-cell lymphoma and immune-mediated diseases, its effects on the immune system beyond apoptosis are largely unknown.

Bone marrow transplantation (BMT), a common cause of GVHD in humans, was used to induce GVHD in mice. In both of the mouse models of GVHD, bone marrow donor and host were identical at the major histocompatibility complex. The models differed by whether the disease was mediated by CD8+ or CD4+ T cells.

A single injection of ECP-treated cells suppressed GVHD and 4 weekly injections improved both survival and GVHD clinical scores, compared with controls injected with either untreated cells or diluent. Mice receiving ECP-treated cells also showed significantly less histopathological damage in all three GVHD target organs (liver, gut and skin) and dramatically improved immune reconstitution 8 weeks after BMT.

In addition, ECP reduced effector T cell responses and generated regulatory T cells from donor cells that had not been directly exposed to MOP-8 and UVA. This increase in regulatory T cells was seen soon after the infusion of ECP-treated cells, remained stable for several weeks and was also shown to be necessary for the reversal of GVHD.

Blood 2008;112:1515-1521. 本人已认领该文编译,48小时后若未提交译文,请其他战友自由认领。 关注中 先学习了 体外光化学细胞疗法可以逆转移植物抗宿主病
NEW YORK (Reuters Health) Sept 05 - Cells treated with extracorporeal photopheresis (ECP) can reverse graft-versus-host disease (GVHD) by increasing donor regulatory T cells and by indirectly reducing the number of donor effector lymphocytes that have not undergone ECP, according to the findings of a study that used two well-established mouse models.
纽约(路透社健康信息)9月5日:根据一项通过以采用的两个良好可信的小鼠模型进行的研究,体外光分离置换法(ECP)的细胞治疗能通过增加供体的调节性T细胞和间接减少供体不经过ECP的效应淋巴细胞来逆转移植物抗宿主病(GVHD)。

"This study is an example of reverse translation. Instead of 'bench to bedside,' we have brought a treatment already used in the clinic back to the laboratory to try to gain insight about how it might work," Dr. Erin Gatza of the University of Michigan Cancer Center, Ann Arbor, told Reuters Health.
“该研究是一个逆翻译的例子。不像‘床边工作台’

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作者:admin@医学,生命科学    2010-12-19 05:11
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