CD27 expression promotes long-term survival of functional effector-memory CD8+ cytotoxic T lymphocytes in HIV-infected patients.

CD27 expression promotes long-term survival of functional effector-memory CD8+ cytotoxic T lymphocytes in HIV-infected patients.
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DOI:
10.1084/jem.20040717
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发表时间:
2004-12-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Greenberg PD
Greenberg PD
中科院分区:
其他
文献类型:
--
作者:
Ochsenbein AF;Riddell SR;Brown M;Corey L;Baerlocher GM;Lansdorp PM;Greenberg PD

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人类免疫缺陷病毒(HIV)特异性CD8+T细胞在HIV感染患者中保持高频率,尽管对病毒的CD4+T辅助反应受损,但与其他分化的效应细胞毒性T细胞不同,大多数继续表达肿瘤坏死因子受体家族成员CD27。由于CD27的配体(CD70)在HIV感染的宿主中也过表达,我们研究了CD27在HIV特异性CD8+T细胞上表达的性质和潜在的功能后果。对来自同一HIV特异性克隆的CD2 7+和CD2 7−T细胞的分析表明,CD2 7的保留不干扰效应功能的获得,并且在T细胞受体刺激后,由CD2 7同时触发的CD2 7+细胞表现出比CD2 7−T细胞更强的抗凋亡、产生白介素2和增殖的能力。在转移回HIV感染者体内后,自体的HIV特异性CD2 7−T细胞迅速消失,但来自同一克隆的CD2 7+T细胞以较高的频率持续存在。我们的发现提示,CD27-CD70在HIV感染中的相互作用可能为CD27+CD8+T细胞提供生存优势,并弥补限制或缺失的CD4+T细胞帮助维持CD8应答。
Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response.
DOI: 10.1084/jem.20030916
发表时间: 2003-11-03
影响因子: 15.3
作者:
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发表时间: 1993-02-01
期刊: The Journal of experimental medicine
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发表时间: 1993-05-07
期刊: CELL
影响因子: 64.5
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发表时间: 1996-10-04
期刊: SCIENCE
影响因子: 56.9
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