Servicio de Hematología, Hospital Universitario de Salamanca and Centro de Investigación del Cáncer/IBMCC (CIC/CSIC) Salamanca, Spain.
Leuk Res. 2011 Oct;35(10):1412-5. doi: 10.1016/j.leukres.2011.05.018. Epub 2011 Jun 11.
Current graft-versus-host disease (GVHD) inhibition approaches lead to abrogation of pathogen-specific T-cell responses. We propose an approach to inhibit GVHD without hampering immunity against pathogens: in vitro depletion of alloreactive T cells with the preoteasome inhibitor bortezomib. We show that PBMCs stimulated with allogeneic cells and treated with bortezomib greatly reduce their ability to produce IFN-γ when re-stimulated with the same allogeneic cells, but mainly preserve their ability to respond to citomegalovirus stimulation. Unlike in vivo administration of immunosuppressive drugs or other strategies of allodepletion, in vitro allodepletion with bortezomib maintains pathogen-specific T cells, representing a promising alternative for GVHD prophylaxis.
目前的移植物抗宿主病（GVHD）抑制方法会导致病原体特异性 T 细胞反应的丧失。我们提出了一种抑制 GVHD 而不损害对病原体免疫力的方法：用蛋白酶体抑制剂硼替佐米体外耗尽同种异体反应性 T 细胞。我们表明，用同种异体细胞刺激的 PBMC 并经硼替佐米处理，当用相同的同种异体细胞再次刺激时，大大降低了产生 IFN-γ 的能力，但主要保留了对巨细胞病毒刺激的反应能力。与体内给予免疫抑制剂或其他同种异体耗竭策略不同，硼替佐米的体外同种异体耗竭维持了病原体特异性 T 细胞，这是一种有前途的 GVHD 预防替代方法。
