Novel method for detection of virus-specific CD41+ T cells indicates a decreased EBV-specific CD4+ T cell response in untreated HIV-infected subjects.
A lower function of EBV-specific CD8(+) T cells in HIV-infected subjects could be related to a lack of specific CD4(+) T cell help. Therefore, we studied EBV-specific CD4(+) T cells in both healthy donors and untreated or highly active antiretroviral therapy (HAART)-treated HIV-seropositive homosexual men. To this end, PBMC were stimulated with overlapping peptide pools from a latent and a lytic EBV protein, EBV nuclear antigen (EBNA)1 and EBV lytic-switch protein ZEBRA (BZLF1), respectively. EBV-specific CD4(+) T cell frequencies measured directly ex vivo were low. To measure EBV-specific memory CD4(+) T cells, capable of both expansion and IFN-gamma production upon antigenic challenge, we developed a specific and reproducible assay, combining ex vivo expansion of specific T cells with flow cytometric analysis of IFN-gamma production. Untreated HIV-infected individuals had a lower CD4(+) T cell response to both EBNA1 and BZLF1 as compared to healthy EBV carriers and HAART-treated HIV-positive subjects. This suggests loss of EBV-specific CD4(+) T cells due to HIV infection, while HAART might restore this response. In addition, we found an increase in the EBNA1-specific CD8(+) T cell response in HAART-treated subjects. Interestingly, numbers of EBV-specific CD4(+) and CD8(+) T cells were inversely correlated with EBV viral load, suggesting an important role also for EBV-specific CD4(+) T cells in the control of EBV infection.
Piriou
Erwan R
ER
Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
van Dort
Karel
K
Nanlohy
Nening M
NM
van Oers
Marinus H
MH
Miedema
Frank
F
van Baarle
Debbie
D
D000328:Adult; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004268:DNA-Binding Proteins / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods*; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D015534:Trans-Activators; D014764:Viral Proteins; D007371:Interferon-gamma