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.
Ochsenbein
Adrian F
AF
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. adrian.ochsenbein@dkf.unibe.ch
Riddell
Stanley R
SR
Brown
Michele
M
Corey
Lawrence
L
Baerlocher
Gabriela M
GM
Lansdorp
Peter M
PM
Greenberg
Philip D
PD
D019264:Adoptive Transfer; D015703:Antigens, CD / Q000502:physiology; D053282:CD27 Ligand; D002470:Cell Survival; D003587:Cytomegalovirus / Q000276:immunology; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis; D008565:Membrane Proteins / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis / Q000502:physiology*
D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7