Restricted TCR repertoire and long-term persistence of donor-derived antigen-experienced CD4+ T cells in allogeneic bone marrow transplantation recipients.
Restricted TCR repertoire and long-term persistence of donor-derived antigen-experienced CD4+ T cells in allogeneic bone marrow transplantation recipients.
复制标题
同种异体骨髓移植受者中受供者来源的抗原经历过的 CD4 T 细胞的 TCR 库有限和长期持续存在。
作者：
M. Vavassori;R. Maccario;A. Moretta;P. Comoli;A. Wack;F. Locatelli;A. Lanzavecchia;E. Maserati;P. Dellabona;G. Casorati;D. Montagna
我们研究了ag经历供体T细胞移植对异体骨髓移植（BMT）受者免疫重建的贡献。为此，我们结合细胞培养方法分离破伤风类毒素（TT）特异性T细胞克隆，并利用TCR N区序列进行敏感和特异性异双工分析以监测特定克隆型的存在。我们记录了BMT后患者对TT的反应很小，完全是由少数供体衍生克隆引起的。这些患者对TT疫苗表现出强烈的多克隆应答；然而，随着移植转移的T细胞克隆在移植后至少5年内仍然可以在多克隆T细胞系中检测到。我们还证明，在BMT之前接种TT的供体导致更相关的ag经历的T细胞转移，允许受体在不需要接种疫苗的情况下产生强烈的多克隆反应。这些发现为为供体接种疫苗以优化保护性T细胞免疫的过继性转移提供了理论依据，并提出了将预防性T细胞过继疗法与骨髓输注结合使用的可能性。
We investigated the contribution of transfer of Ag-experienced donor T cells to the immune reconstitution of allogeneic bone marrow transplantation (BMT) recipients. To this purpose, we used a combination of cell culture methods to isolate tetanus toxoid (TT)-specific T cell clones, and a sensitive and specific heteroduplex analysis to monitor the presence of a particular clonotype using TCR N region sequences. We document that patients after BMT display a small response to TT, entirely accounted for by few donor-derived clones. These patients show a strong polyclonal response to TT vaccination; however, the T cell clones transferred with the transplant can still be detected within the polyclonal T cell lines for up to at least 5 yr after BMT. We also demonstrate that vaccination of donors with TT before BMT results in a more relevant transfer of Ag-experienced T cells, allowing the recipients to mount a strong polyclonal response without need of vaccination. These findings provide a rationale for vaccinating donors to optimize adoptive transfer of protective T cell immunity into recipients, and suggest the possibility of using preventive T cell adoptive therapy in conjunction with marrow infusion.