Novel method for detection of virus-specific CD4 super(+) T cells indicates a decreased EBV-specific CD4 super(+) T cell response in untreated HIV-infected subjects

• Published in: European journal of immunology 2005-01, Vol.35 (3), p.796-805
• Main Authors: Piriou, Erwan R, Van Dort, Karel, Nanlohy, Nening M, Van Oers, Marinus H, Miedema, Frank, Van Baarle, Debbie
• Format: Article
• Language: English
• Subjects: Epstein-Barr virus; Human immunodeficiency virus
• ISSN: 0014-2980
• DOI: 10.1002/eji.200425792

A lower function of EBV-specific CD8 super(+) T cells in HIV-infected subjects could be related to a lack of specific CD4 super(+) T cell help. Therefore, we studied EBV-specific CD4 super(+) 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 super(+) T cell frequencies measured directly ex vivo were low. To measure EBV-specific memory CD4 super(+) 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 super(+) 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 super(+) T cells due to HIV infection, while HAART might restore this response. In addition, we found an increase in the EBNA1-specific CD8 super(+) T cell response in HAART-treated subjects. Interestingly, numbers of EBV-specific CD4 super(+) and CD8 super(+) T cells were inversely correlated with EBV viral load, suggesting an important role also for EBV-specific CD4 super(+) T cells in the control of EBV infection.