Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Cell Immunol. 2018 Oct;332:129-133. doi: 10.1016/j.cellimm.2018.07.011. Epub 2018 Jul 30.
GARP is a transmembrane protein that presents latent TGF-β1 on the surface of regulatory T cells (Tregs). Neutralizing anti-GARP monoclonal antibodies that prevent the release of active TGF-β1, inhibit the immunosuppressive activity of human Tregs in vivo. In this study, we investigated the contribution of GARP on mouse Tregs to immunosuppression in experimental tumors. Unexpectedly, Foxp3 conditional garp knockout (KO) mice challenged orthotopically with GL261 tumor cells or subcutaneously with MC38 colon carcinoma cells did not show prolonged survival or delayed tumor growth. Also, the suppressive function of KO Tregs was similar to that of wild type Tregs in the T cell transfer model in allogeneic, immunodeficient mice. In conclusion, garp deletion in mouse Tregs is not sufficient to impair their immunosuppressive activity in vivo.
GARP 是一种跨膜蛋白，可将潜伏的 TGF-β1 呈现在调节性 T 细胞（Tregs）的表面。中和抗 GARP 单克隆抗体可阻止活性 TGF-β1 的释放，从而抑制体内人 Tregs 的免疫抑制活性。在这项研究中，我们研究了 GARP 在实验性肿瘤中的小鼠 Tregs 对免疫抑制的贡献。出乎意料的是，Foxp3 条件性 garp 敲除（KO）小鼠接受 GL261 肿瘤细胞的原位挑战或 MC38 结肠癌细胞的皮下接种后，并未表现出延长的存活或肿瘤生长延迟。此外，在同种异体免疫缺陷小鼠的 T 细胞转移模型中，KO Tregs 的抑制功能与野生型 Tregs 相似。总之，在体内，GARP 缺失不足以损害小鼠 Tregs 的免疫抑制活性。
