The Journal of Experimental Medicine
Aegean Conferences: 2009 Conferences
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Published 6 December 2004. doi:10.1084/jem.20040717
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 11, 1407-1417
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CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+ Cytotoxic T Lymphocytes in HIV-infected Patients

Adrian F. Ochsenbein1, Stanley R. Riddell1,4, Michele Brown1, Lawrence Corey1,4, Gabriela M. Baerlocher2, Peter M. Lansdorp2,3, and Philip D. Greenberg1,4,5

1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
2 Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3
3 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4E3
4 Department of Medicine, University of Washington, Seattle, WA 98195
5 Department of Immunology, University of Washington, Seattle, WA 98195

Address correspondence to Adrian F. Ochsenbein, Dept. of Clinical Research and Institute for Medical Oncology, University of Berne, Murtenstrasse 35, 3010 Berne, Switzerland. Phone: 41-31-632-4114; Fax: 41-31-632-3297; email: adrian.ochsenbein{at}dkf.unibe.ch; or Philip D. Greenberg, University of Washington, BB1325 Health Sciences Building, Box 356527, Seattle, WA 98195. Phone: (206) 543-8306; Fax: (206) 685-3128; email: pgreen{at}u.washington.edu

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.

Key Words: adoptive immunotherapy • viruses • immunologic memory • TNFR • IL-2

Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate succinimidyl ester; LCL, lymphoblastoid cell line.


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