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 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.