Depletion of alloreactive T-cells in vitro using the proteasome inhibitor bortezomib preserves the immune response against pathogens
Depletion of alloreactive T-cells in vitro using the proteasome inhibitor bortezomib preserves the immune response against pathogens
复制标题
DOI：
10.1016/j.leukres.2011.05.018
复制
发表时间：
2011-10-01
影响因子：
2.7
通讯作者：
Antonio Perez-Simon, Jose
中科院分区：
文献类型：
--
作者：
Blanco, Belen;Ignacio Sanchez-Abarca, Luis;Antonio Perez-Simon, Jose
目前的移植物抗宿主病（GVHD）抑制方法导致病原体特异性t细胞反应的消除。我们提出了一种抑制GVHD而不妨碍对病原体免疫的方法：用前溶酶体抑制剂硼替佐米体外消耗同种异体反应性T细胞。我们发现，用同种异体细胞刺激PBMCs并用硼替佐米处理后，当用同种异体细胞再次刺激时，PBMCs产生ifn - γ的能力大大降低，但主要保留了它们对citomegalovirus刺激的反应能力。与体内施用免疫抑制药物或其他同种异体清除策略不同，硼替佐米体外同种异体清除可以维持病原体特异性T细胞，这是预防GVHD的一种有希望的替代方法。(C) 2011 Elsevier Ltd.版权所有。
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-gamma 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. (C) 2011 Elsevier Ltd. All rights reserved.