CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

AF Ochsenbein, SR Riddell, M Brown… - The Journal of …, 2004 - rupress.org
AF Ochsenbein, SR Riddell, M Brown, L Corey, GM Baerlocher, PM Lansdorp
The Journal of experimental medicine, 2004rupress.org
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 …
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.
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