Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
J Immunol. 2010 Aug 1;185(3):1920-6. doi: 10.4049/jimmunol.0902217. Epub 2010 Jun 23.
We previously showed that transplantation with IL-21R gene-deficient splenocytes resulted in less severe graft-versus-host disease (GVHD) than was observed with wild type splenocytes. In this study, we sought to find mechanism(s) explaining this observation. Recipients of donor CD4(+) T cells lacking IL-21R exhibited diminished GVHD symptoms, with reduced inflammatory cell infiltration into the liver and intestine, leading to prolonged survival. After transplantation, CD4(+) T cell numbers in the spleen were reduced, and MLR and cytokine production by CD4(+) T cells were impaired. These results suggest that IL-21 might promote GVHD through enhanced production of effector CD4(+) T cells. Moreover, we found that CD25 depletion altered neither the impaired MLR in vitro nor the ameliorated GVHD symptoms in vivo. Thus, the attenuated GVHD might be caused by an impairment of effector T cell differentiation itself, rather than by an increase in regulatory T cells and suppression of effector T cells.
我们之前的研究表明，与野生型脾细胞相比，移植缺乏白细胞介素 21 受体（IL-21R）基因的脾细胞导致移植物抗宿主病（GVHD）的严重程度降低。在这项研究中，我们试图寻找解释这一观察结果的机制。与野生型脾细胞相比，缺乏 IL-21R 的供体 CD4+T 细胞的受体表现出 GVHD 症状减轻，肝脏和肠道的炎症细胞浸润减少，导致存活时间延长。移植后，脾中 CD4+T 细胞数量减少，混合淋巴细胞反应（MLR）和 CD4+T 细胞的细胞因子产生受损。这些结果表明，IL-21 可能通过增强效应 CD4+T 细胞的产生来促进 GVHD。此外，我们发现 CD25 耗竭既没有改变体外受损的 MLR，也没有改善体内 GVHD 症状。因此，减轻的 GVHD 可能是由于效应 T 细胞分化本身受损，而不是由于调节性 T 细胞增加和效应 T 细胞抑制所致。
