Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo
Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo
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DOI：
10.1182/blood-2007-08-106526
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发表时间：
2008-02-01
期刊：
影响因子：
20.3
通讯作者：
Garman, Richard D.
中科院分区：
文献类型：
--
作者：
Ruzek, Melanie C.;Waire, James S.;Garman, Richard D.
抗胸腺细胞/抗淋巴细胞球蛋白是临床上用于治疗急性移植排斥反应的多克隆抗人t细胞抗体。这些试剂消耗T细胞，但兔抗人胸腺细胞球蛋白也被证明在体外诱导调节性T细胞。为了研究抗胸腺细胞球蛋白诱导的调节细胞在体内是否具有功能，我们制备了相应的兔抗尿胸腺细胞球蛋白（mATG），并测试了其在体外诱导调节细胞的能力，以及这些细胞在过继转移后是否能在体内抑制急性移植物抗宿主病（GVHD）。在体外，mATG诱导CD4(+)CD25(+) T细胞群表达几种代表调节性T细胞的细胞表面分子。这些细胞既不表达Foxp3蛋白，也不表达mRNA，但在体外和体内均表现出抑制功能，并将其过继转移到GVHD模型中。这些结果表明，在小鼠系统中，抗胸腺细胞球蛋白诱导具有抑制活性的细胞，在体内也具有保护急性GVHD的功能。因此，在小鼠和人类系统中，抗胸腺细胞球蛋白不仅消耗T细胞，而且似乎还产生调节细胞。抗胸腺细胞球蛋白在体外产生调节细胞可以为免疫介导性疾病提供额外的治疗方式。（《血液》，2008;111:1726-1734）。(C) 2008年由美国血液病学会出版。
Antithymocyte/antliymphocyte globulins are polyclonal antihuman T-cell antibodies used clinically to treat acute transplant rejection. These reagents deplete T cells, but a rabbit antihuman thymocyte globulin has also been shown to induce regulatory T cells in vitro. To examine whether antithymocyte globulin-induced regulatory cells might be functional in vivo, we generated a corresponding rabbit antimurine thymocyte globulin (mATG) and tested its ability to induce regulatory cells in vitro and whether those cells can inhibit acute graft-versus-host disease (GVHD) in vivo upon adoptive transfer. In vitro, mATG induces a population of CD4(+)CD25(+) T cells that express several cell surface molecules representative of regulatory T cells. These cells do not express Foxp3 at either the protein or mRNA level, but do show suppressive function both in vitro and in vivo when adoptively transferred into a model of GVHD. These results demonstrate that in a murine system, antithymocyte globulin induces cells with suppressive activity that also function in vivo to protect against acute GVHD. Thus, in both murine and human systems, antithymocyte globulins not only deplete T cells, but also appear to generate regulatory cells. The in vitro generation of regulatory cells by antithymocyte globulins could provide additional therapeutic modalities for immune-mediated disease. (Blood. 2008; 111:1726-1734). (C) 2008 by The American Society of Hematology.