CD4+CD25+Foxp3+IFNγ+ Treg are immunosuppressive in vitro and increase with intensity of the alloresponse in pretransplant MLC
CD4+CD25+Foxp3+IFNγ+ Treg are immunosuppressive in vitro and increase with intensity of the alloresponse in pretransplant MLC
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DOI：
10.1016/j.trim.2012.08.003
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发表时间：
2012-10-01
影响因子：
1.5
通讯作者：
Opelz, Gerhard
中科院分区：
文献类型：
--
作者：
Daniel, Volker;Sadeghi, Mahmoud;Opelz, Gerhard
Phorbol-12-myristate-13-acetate(PMA)/Ionomycin或同种异体抗原刺激分离的CD3(+)、CD4(+)、CD25(+)、Foxp3(+)诱导的Treg在长期肾功能良好的患者中较受损患者更容易被检测到。此外，我们还研究了移植前从PMA/离子霉素刺激的健康人PBL中分离的CD25(+)干扰素γ(+)PBL抑制自体PBL的继代细胞培养的iTreg诱导和细胞增殖。此外，从原代MLC中分离的CD4(+)CD25(+)干扰素γ(+)PBL可非特异性地抑制继发性MLC中同种异体T细胞的激活，而与刺激细胞无关。然而，在特定的MLC中观察到最强的抑制作用。长期移植效果差的患者能够在移植前的MLC中形成干扰素-γ(+)iTreg。研究对象为8例移植后18~29年血肌酐水平在0.9~14 mg/dl之间的患者。在移植前获得受者和供者细胞的多细胞肺癌中，强干扰素-γ(+)iTreg(p=0.007)和强原始细胞诱导(p=0.047)与受损的长期移植结果相关。在以第三方细胞为刺激物的非特异性MLC中，长期移植结果与细胞增殖和iTreg诱导无关。数据表明，长期移植效果受损的患者在特定的移植前MLC中能够形成大量的干扰素-γ(+)iTreg。诱导干扰素-γ(+)iTreg的数量取决于同种异体反应的强度，这两个参数与长期移植结果呈负相关。(C)2012爱思唯尔B.V.保留所有权利。
IFN gamma-producing CD3(+)CD4(+)CD25(+)Foxp3(+) induced Treg are more frequently detectable in patients with good than in patients with impaired long-term kidney graft function.We investigated the in-vitro function of separated CD3(+)CD4(+)CD25(+)Foxp3(+)IFN gamma(+) PBL that were induced by phorbol-12-myristate-13-acetate(PMA)/Ionomycin or alloantigenic stimulation. Additionally, we studied iTreg induction and cell proliferation in MLC with pretransplant obtained PBLCD4(+)CD25(+)IFN gamma(+) PBL separated from PMA/Ionomycin-stimulated PBL of healthy controls inhibited secondary cell cultures of autologous PBL Furthermore, CD4(+)CD25(+)IFN gamma(+) PBL separated from primary MLC and added to secondary MLC suppressed allogeneic T-cell activation in secondary MLC unspecifically, irrespective of the stimulator cell. However, the strongest suppression was observed in specific MLC. Patients with poor long-term graft outcome were able to form IFN gamma(+) iTreg in pretransplant MLC. Eight patients with a serum creatinine level ranging from 0.9 to 14 mg/dl 18-29 years posttransplant were studied. In MLC with pretransplant obtained recipient and donor cells, strong IFN gamma(+) iTreg (p = 0.007) and strong blast induction (p = 0.047) were associated with impaired long-term graft outcome. Long-term graft outcome was not associated with cell proliferation and iTreg induction in unspecific MLC with third-party cells as stimulator.The data indicate that patients with impaired long-term graft outcome are able to form high numbers of IFN gamma(+) iTreg in specific pretransplant MLC. Quantity of induced IFN gamma(+) iTreg depends on the strength of the alloresponse and both parameters are inversely associated with long-term graft outcome. (C) 2012 Elsevier B.V. All rights reserved.