GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T cells in graft-versus-host disease.
GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T cells in graft-versus-host disease.
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DOI：
10.1084/jem.20040116
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发表时间：
2004-07-19
期刊：
影响因子：
--
通讯作者：
Van Den Brink MR
中科院分区：
文献类型：
--
作者：
Muriglan SJ;Ramirez-Montagut T;Alpdogan O;Van Huystee TW;Eng JM;Hubbard VM;Kochman AA;Tjoe KH;Riccardi C;Pandolfi PP;Sakaguchi S;Houghton AN;Van Den Brink MR
糖皮质激素诱导的肿瘤坏死因子受体家族相关基因（GITR）是肿瘤坏死因子受体（TNFR）家族的成员，其在未刺激的T细胞、B细胞和巨噬细胞上以低水平表达。活化后，CD 4+和CD 8 + T细胞上调GITR表达，而免疫调节性T细胞组成型表达高水平的GITR。在这里，我们表明，GITR可以调节同种异体骨髓移植（BMT）后移植物抗宿主病（GVHD）的同种反应性反应。使用主要组织相容性复合物I类和II类差异的BMT模型，我们证明了GITR刺激在体外和体内增强同种异体反应性CD 8 + CD 25 − T细胞增殖，而减少同种异体反应性CD 4 + CD 25 −增殖。同种异体刺激的CD 4 + CD 25 −细胞在GITR刺激后表现出依赖于Fas-FasL途径的凋亡增加。在存在GITR激活抗体（Ab）的情况下，含有CD 8 + CD 25-供体T细胞的同种异体移植物的受体的GVHD发病率和死亡率增加。相反，当用GITR激活抗体治疗时，具有CD 4 + CD 25 − T细胞的同种异体移植物的受体显示出GVHD的显著降低。我们的研究结果表明，GITR对同种异体反应性CD 4+和CD 8 + T细胞的调节具有相反的作用。
Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4+ and CD8+ T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8+CD25− T cell proliferation, whereas it decreases alloreactive CD4+CD25− proliferation. Allo-stimulated CD4+CD25− cells show increased apoptosis upon GITR stimulation that is dependent on the Fas–FasL pathway. Recipients of an allograft containing CD8+CD25− donor T cells had increased GVHD morbidity and mortality in the presence of GITR-activating antibody (Ab). Conversely, recipients of an allograft with CD4+CD25− T cells showed a significant decrease in GVHD when treated with a GITR-activating Ab. Our findings indicate that GITR has opposite effects on the regulation of alloreactive CD4+ and CD8+ T cells.
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影响因子：
2.2
作者：
LYONS, AB;PARISH, CR
通讯作者：
PARISH, CR
影响因子：
4.4
作者：
Kohm, AP;Williams, JS;Miller, SD
通讯作者：
Miller, SD
供体型CD4（+）CD25（+）调节性T细胞在同种异体骨髓移植后抑制致命的急性移植物抗宿主疾病。
影响因子：
15.3
作者：
Hoffmann, Petra;Ermann, Joerg;Edinger, Matthias;Fathman, C Garrison;Strober, Samuel
通讯作者：
Strober, Samuel
影响因子：
4
作者：
Lee, HS;Shin, HH;Choi, HS
通讯作者：
Choi, HS
影响因子：
9.2
作者：
Gurney, AL;Marsters, SA;Ashkenazi, A
通讯作者：
Ashkenazi, A