Lack of Epstein-Barr virus- and HIV-specific CD27- CD8+ T cells is associated with progression to viral disease in HIV-infection.
OBJECTIVE
Despite readily detectable virus-specific CD8+ T cells in most HIV-infected patients, immune surveillance is eventually lost, leading to progression to AIDS. To investigate the underlying mechanism of this loss of immune control phenotypic analysis of HIV- and Epstein-Barr virus (EBV)-specific CD8+ T cells was performed.


METHODS
In three clinically distinct groups, long-term asymptomatics, progressors to opportunistic infections and progressors to EBV-associated non-Hodgkin lymphoma's (NHL), both number and phenotype of virus-specific CD8+ T cells was studied longitudinally.


METHODS
The number of HIV- and EBV-specific T cells were determined using HLA-peptide tetrameric complexes. The phenotype of these virus-specific T cells was investigated by costaining with CD27 and CD45RO and thereby identifying specific subsets of CD8+ T cells.


RESULTS
Individuals co-infected with HIV and EBV persistently had low numbers of HIV-specific CD27- T cells, in contrast to rising numbers of EBV-specific CD27- CD8+ T cells. However, HIV-infected individuals developing EBV-associated AIDS-related NHL had very low numbers of EBV-specific CD27- CD8+ T cells. Higher numbers of HIV-specific CD27- CD8+ T cells were associated with delayed disease progression. Virus-specific CD27- T cells, compared with CD27+ T cells showed elevated interferon-gamma production in response to viral peptides in vitro, indicative for strong effector function.


CONCLUSIONS
Taken together, our data indicate that virus-specific CD27- T cells may be important effector T cells in controlling chronic viral infections in humans and that lack of differentiation into CD27- effector T cells may lead to progression of viral disease.
van Baarle
Debbie
D
Department of Clinical Viro-Immunology, CLB/Sanquin & Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, The Netherlands. d_van_baarle@clb.nl
Kostense
Stefan
S
Hovenkamp
Egbert
E
Ogg
Graham
G
Nanlohy
Nening
N
Callan
Margaret F C
MF
Dukers
Nicole H T M
NH
McMichael
Andrew J
AJ
van Oers
Marinus H J
MH
Miedema
Frank
F
D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma