Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease.
Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease.
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DOI：
10.1371/journal.pone.0145763
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Meyer E
中科院分区：
文献类型：
--
作者：
Florek M;Schneidawind D;Pierini A;Baker J;Armstrong R;Pan Y;Leveson-Gower D;Negrin R;Meyer E
在同种异体造血细胞移植（HCT）的鼠模型中过继转移CD 4 + CD 25 + Foxp 3+调节性T细胞（T细胞）已显示出保护受体小鼠免于致死性急性移植物抗宿主病（GVHD），并且该方法正在人体临床试验中积极研究。在这里，我们研究了冷冻保存对TCFs的影响。我们发现，小鼠和人TclO的冷冻和解冻与L-选择素（CD 62 L）的表达减少有关，这是先前确定的有助于TclO体内保护作用的重要因素。冷冻和解冻的小鼠THBE显示出体外与CD 62 L结合伴侣MADCAM 1结合的能力降低，以及体内向次级淋巴器官的归巢受损。过继转移后，冷冻和解冻的THBE未能保护免受致命的GVHD相比，新鲜THBE在小鼠模型中的同种异体HCT跨越主要组织相容性屏障。总之，直接施用过继转移的冷冻和解冻的Treg不利地影响其免疫抑制潜力，这是在Treg免疫疗法的临床实施中考虑的重要因素。
The adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in murine models of allogeneic hematopoietic cell transplantation (HCT) has been shown to protect recipient mice from lethal acute graft-versus-host disease (GVHD) and this approach is being actively investigated in human clinical trials. Here, we examined the effects of cryopreservation on Tregs. We found that freeze and thaw of murine and human Tregs is associated with reduced expression of L-selectin (CD62L), which was previously established to be an important factor that contributes to the in vivo protective effects of Tregs. Frozen and thawed murine Tregs showed a reduced capacity to bind to the CD62L binding partner MADCAM1 in vitro as well as an impaired homing to secondary lymphoid organs in vivo. Upon adoptive transfer frozen and thawed Tregs failed to protect against lethal GVHD compared with fresh Tregs in a murine model of allogeneic HCT across major histocompatibility barriers. In summary, the direct administration of adoptively transferred frozen and thawed Tregs adversely affects their immunosuppressive potential which is an important factor to consider in the clinical implementation of Treg immunotherapies.