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更昔洛韦治疗巨细胞病毒感染期间的病毒逃逸与T细胞免疫:一例胰肾移植受者的病例报告

Viral escape and T-cell immunity during ganciclovir treatment of cytomegalovirus infection: case report of a pancreatico-renal transplant recipient.

作者信息

Benz Christine, Holz Gisela, Michel Detlef, Awerkiew Sabine, Dries Volker, Stippel Dirk, Goeser Tobias, Busch Dirk H

机构信息

Department of Gastroenterology, University of Cologne, Cologne, Germany. Christine.

出版信息

Transplantation. 2003 Mar 15;75(5):724-7. doi: 10.1097/01.TP.0000052664.18029.E6.

Abstract

BACKGROUND

Pancreas-kidney transplant recipients are at high risk for cytomegalovirus (CMV) disease despite prophylactic ganciclovir therapy. Because the impact of antiviral therapy on anti-CMV immune reactions is unknown, CMV-specific T-cell subsets in primary and recurrent CMV infection were analyzed in a pancreas-kidney transplant case study.

METHODS

Major histocompatibility complex class I tetramers were used to detect peripheral CMV pp65-specific CD8 T cells. Intracellular cytokine staining was used to determine the frequency of CMV-specific CD4 T cells. Conventional virologic parameters and routine laboratory parameters were monitored. For ganciclovir resistance testing, CMV-UL97 genotyping was performed.

RESULTS

Despite prophylactic ganciclovir therapy, primary CMV infection induced in vivo expansion of activated CMV-specific CD8 T cells. Interestingly, viral dissemination during recurrent CMV disease was a result of partially ganciclovir-resistant CMV. Recovery after discontinued ganciclovir treatment was associated with the expansion of CMV-specific CD4 T cells.

CONCLUSION

Immunologic monitoring may contribute to clinical management of recurrent CMV disease.

摘要

背景

尽管接受了更昔洛韦预防性治疗,但胰腺-肾脏移植受者仍有患巨细胞病毒(CMV)疾病的高风险。由于抗病毒治疗对CMV特异性免疫反应的影响尚不清楚,因此在一项胰腺-肾脏移植病例研究中分析了原发性和复发性CMV感染中的CMV特异性T细胞亚群。

方法

使用主要组织相容性复合体I类四聚体检测外周血中CMV pp65特异性CD8 T细胞。采用细胞内细胞因子染色法测定CMV特异性CD4 T细胞的频率。监测常规病毒学参数和常规实验室参数。为进行更昔洛韦耐药性检测,对CMV-UL97进行基因分型。

结果

尽管接受了更昔洛韦预防性治疗,但原发性CMV感染仍诱导体内活化的CMV特异性CD8 T细胞扩增。有趣的是,复发性CMV疾病期间的病毒播散是部分耐更昔洛韦的CMV所致。停用更昔洛韦治疗后的恢复与CMV特异性CD4 T细胞的扩增有关。

结论

免疫监测可能有助于复发性CMV疾病的临床管理。

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