Association of multispecific CD4(+) response to hepatitis C and severity of recurrence after liver transplantation.
Association of multispecific CD4(+) response to hepatitis C and severity of recurrence after liver transplantation.
复制标题
对丙型肝炎的多特异性 CD4( ) 反应与肝移植后复发严重程度的关联。
DOI：
10.1016/s0016-5085(99)70352-5
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发表时间：
1999
期刊：
影响因子：
29.4
通讯作者：
Bouwer,HG
中科院分区：
文献类型：
--
作者：
Rosen,HR;Hinrichs,DJ;Gretch,DR;Koziel,MJ;Chou,S;Houghton,M;Rabkin,J;Corless,CL;Bouwer,HG
背景与目的丙型肝炎病毒（HCV）感染肝移植后，移植物易发生再感染。间接证据表明，细胞免疫反应可能发挥核心作用。本分析的目的是确定HCV特异性外周血CD 4 + T细胞反应和肝移植后复发的严重程度之间的相关性。Methods 58例HCV血清阳性患者，包括43例肝移植受者，至少1年的组织学随访，进行了研究。外周血单个核细胞（PBMC）从新鲜肝素化的血液中分离和刺激与重组HCV抗原（核心，E2，NS 3，NS 4和NS 5）或对照antigens.Results14（40%）的35例轻度或无组织学复发的证据，在他们的同种异体移植物中至少有1个HCV抗原。11例对NS 3应答，5例对所有非结构抗原应答，3例仅对HCV核心多肽应答。相比之下，在8例严重的HCV复发，没有增殖反应的任何HCV抗原被视为（P = 0.03），尽管响应对照antigens.ConclusionsDespite免疫抑制，HCV特异性，主要组织相容性复合物II类限制性CD 4 + T细胞反应是检测肝移植后组织学复发最小的患者。相比之下，来自具有严重HCV复发的患者的PBMC尽管能够响应于非HCV抗原而增殖，但不能响应于HCV抗原。这些发现表明，不能产生病毒特异性T细胞反应在肝移植后HCV相关移植物损伤的发病机制中起着重要作用。我们希望，与复发性HCV相关的免疫调节机制的进一步表征将为新的治疗策略提供理论基础，并减少不可避免的移植物丢失的发生率。《胃肠病学》1999;117：926-932
Background & AimsAfter liver transplantation for hepatitis C virus (HCV), reinfection of the allograft invariably occurs. Indirect evidence suggests that the cellular immune response may play a central role. The purpose of this analysis was to determine the correlation between HCV-specific peripheral CD4+T-cell responses and the severity of recurrence after liver transplantation.MethodsFifty-eight HCV-seropositive patients, including 43 liver transplant recipients with at least 1 year of histological follow-up, were studied. Peripheral blood mononuclear cells (PBMCs) were isolated from fresh heparinized blood and stimulated with either recombinant HCV antigens (core, E2, NS3, NS4, and NS5) or control antigens.ResultsFourteen (40%) of 35 patients with mild or no evidence of histological recurrence within their allografts responded to at least 1 of the HCV antigens. Eleven responded to NS3, 5 to all the nonstructural antigens, and 3 to the HCV core polypeptide alone. In contrast, in the 8 patients with severe HCV recurrence, no proliferation in response to any of the HCV antigens was seen (P = 0.03) despite responses to the control antigens.ConclusionsDespite immunosuppression, HCV-specific, major histocompatibility complex class II–restricted CD4+T-cell responses are detectable in patients with minimal histological recurrence after liver transplantation. In contrast, PBMCs from patients with severe HCV recurrence, despite being able to proliferate in response to non-HCV antigens, fail to respond to the HCV antigens. These findings suggest that the inability to generate virus-specific T-cell responses plays a contributory role in the pathogenesis of HCV-related graft injury after liver transplantation. It is hoped that further characterization of the immunoregulatory mechanisms related to recurrent HCV will provide the rationale for novel therapeutic strategies and diminish the incidence of inevitable graft loss. GASTROENTEROLOGY 1999;117:926-932