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

被引:106
作者
Ochsenbein, AF
Riddell, SR
Brown, M
Corey, L
Baerlocher, GM
Lansdorp, PM
Greenberg, PD
机构
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA
[2] BC Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[3] Univ British Columbia, Dept Med, Vancouver, BC V5Z 4E3, Canada
[4] Univ Washington, Dept Med, Seattle, WA 98195 USA
[5] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
关键词
adoptive immunotherapy; viruses; immunologic memory; TNFR; IL-2;
D O I
10.1084/jem.20040717
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human immunodeficiency virus (HIV)-specific CD8(+) T cells persist in high frequency in HIV-infected patients despite impaired CD4(+) T helper reponse to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumour 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 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 function, and that after T cell receptor simulation, 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, autologus HIV-specific CD27(-) T cells rapidly disappeared. but CD27(-) 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.
引用
收藏
页码:1407 / 1417
页数:11
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