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 infectio

Altered EBV viral load setpoint after HIV seroconversion is in accordance with lack of predictive value of EBV load for the occurrence of AIDS-related non-Hodgkin lymphoma

In contrast to the situation in the post-transplant setting, in HIV-infected individuals an elevated EBV load is not predictive of EBV-related malignancies. To study whether a high EBV load is already a normal situation early in HIV infection and is not related to a decrease in immune function over time, we investigated EBV load and EBV-specific CD8(+) T cells similar to1 year before and I year after HIV seroconversion. EBV load significantly increased after HIV seroconversion from 205 to 1002 copies/10(6) PBMC (p <0.001), whereas no further increase in EBV load was observed between 1 and 5 years after HIV seroconversion (median, 1827-2478 copies/10(6) PBMC; p = 0.530). Interestingly, the absolute number of EBV lytic epitope, RAKFKQLL-specific CD8(+) T cells increased over HIV seroconversion (4.78 to 9.54/mul; p = 0.011). Furthermore, the fraction of CD27-negative effector, RAK-specific CD8(+) T cells tended to increase (from 12.2 to 17.31% CD27(-); p = 0.051), in accordance with Ag-driven differentiation. In conclusion, both virological and immunological data support the idea that a new EBV viral setpoint is reached early in HIV infection, probably by EBV reactivation, as suggested by the preferential increase in EBV lytic epitope-specific CD8(+) T cells. These data may thus help to explain the lack of predictive value of EBV load for the occurrence of AIDS-related lymphom

Detailed kinetics of EBV-specific CD4+ and CD8+ T cells during primary EBV infection in a kidney transplant patient

The etiology of infectious mononucleosis is poorly understood and usually detected many weeks after infection. Here, we present a unique case of primary symptomatic EBV infection after kidney transplantation, in whom we analyzed both EBV-specific CD4+ and CD8+ T cells in detail from the moment of infection up to latency. We show that EBV-specific T-cell responses in peripheral blood during primary EBV infection after kidney transplantation peaked early after the appearance of viral load, but well before onset of IM symptoms, suggesting that IM in this case is not caused by high numbers of CD8+ T cells per se but may be caused by lack of homing to lymph nodes or tonsil