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

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.