Kellner Joshua N, Yvon Eric, Parmar Simrit
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medicine, Hematology and Oncology, George Washington University School of Medicine, Washington, D.C, USA.
Oncotarget. 2018 Sep 14;9(72):33694-33701. doi: 10.18632/oncotarget.26097.
Regulatory T cells (Tregs) are an important component of the immune system involved in regulation of immune cell proliferation and inflammatory responses and preventing autoimmune diseases. The use of Tregs in cellular therapy has recently been explored in clinical trials specifically evaluating the role of expanded Tregs in the prevention of graft-versus-host disease during stem cell transplantation. The possibility of Treg use in the clinic requires clinical grade expansion of Tregs for development of cell therapy protocols and proper homing of Tregs to the intended target. Here we demonstrate a novel medium composition to expand CB Tregs, specifically upregulation the homing and activation markers CD62L and cutaneous lymphocyte antigen (CLA). CLA expression was uniquely acquired during activation of Tregs with subsequent loss or lack of expression with media change. This finding highlights the importance of proper growth conditions unique to Tregs that can alter expression of proteins and establishes a baseline for expanding marker specific Tregs that home and target unique tissues.
调节性T细胞(Tregs)是免疫系统的重要组成部分,参与调节免疫细胞增殖和炎症反应,并预防自身免疫性疾病。最近在临床试验中探索了Tregs在细胞治疗中的应用,这些试验专门评估了扩增的Tregs在干细胞移植过程中预防移植物抗宿主病的作用。Tregs在临床上的应用可能性需要对Tregs进行临床级别的扩增,以制定细胞治疗方案,并使Tregs正确归巢到预期靶点。在这里,我们展示了一种用于扩增脐血Tregs的新型培养基组合物,特别是上调归巢和激活标志物CD62L和皮肤淋巴细胞抗原(CLA)。CLA表达是在Tregs激活过程中独特获得的,随后随着培养基的更换而表达丧失或缺乏。这一发现突出了Tregs特有的合适生长条件的重要性,这些条件可以改变蛋白质的表达,并为扩增归巢和靶向独特组织的标志物特异性Tregs建立了基线。