Estimation of human herpesvirus 8 prevalence in high-risk patients by analysis of humoral and cellular immunity.

BACKGROUND: Immunocompromized individuals, such as patients with end-stage renal disease, transplant recipients, and HIV-infected patients, are at increased risk of acquiring human herpesvirus (HHV)-8 associated infectious complications. The prevalence of HHV-8 infection generally is determined by detection of immunoglobulin G. However, because serological assays differ greatly, estimations on the actual HHV-8 prevalence vary considerably. METHODS: HHV-8-specific cellular and humoral immunity were analyzed in 128 controls, 73 patients on dialysis, 67 transplant recipients, and 69 HIV-infected patients with the use of flow cytometry and indirect immunofluorescence microscopy. RESULTS: A higher seroprevalence (from 13.7% to 44.9%) was confirmed for all groups of immunocompromised individuals as compared with healthy controls (3.9%). Among immunocompetent individuals, as little as 12.5% had HHV-8 reactive T-cell frequencies greater than the detection limit. In line with a higher seroprevalence in immunosuppressed patients, HHV-8-specific T cells were detectable in 30.1% of dialysis patients, 20.9% of transplant recipients, and 24.6% of HIV-infected individuals. When combining the individual presence of either HHV-8-specific antibodies or T cells or both, the prevalence of HHV-8 infection approached 15.6% in healthy individuals and 41.1%, 40.3%, and 55.1% in dialysis patients, transplant recipients, and HIV-infected individuals, respectively. CONCLUSIONS: The exclusive serological analysis considerably underestimates the prevalence of HHV-8 infection in all study groups. Thus, the combined quantitation of both humoral and cellular immunity may instead be a superior method to assign the individual HHV-8 status. Moreover, this study suggests that the relative contributions of humoral and cellular immunity in control of HHV-8 may be different depending on the type of immunodeficiency.

Maintenance of HIV-specific central and effector memory CD4 and CD8 T cells requires antigen persistence.

The HIV-specific central and effector CD4 and CD8 memory T cell populations disappear from the peripheral blood of infected individuals under highly active antiretroviral therapy (HAART) with a mean half-life of 6.0 and 7.7 months, respectively. By contrast, cytomegalovirus (CMV)-specific responses are stable or increase. The striking quantitative differences between T cell memory to two persistent viral infections are instructive as to how antigen dosage contributes to the maintenance of antigen-specific memory T cell responses in humans.

The fraction of perforin-expressing HIV-specific CD8 T cells is a marker for disease progression in HIV infection.

OBJECTIVE: Perforin is an important component of the death machinery of cytotoxic T cells (CTL). To evaluate functional differences between HIV- and cytomegalovirus (CMV)-specific CTL of coinfected patients, the frequencies of the respective perforin-expressing T cells were analysed in a rapid whole blood assay. METHODS: Whole blood of HIV- and CMV-infected individuals was specifically stimulated by HIV-1 Pr55(gag) or complete CMV antigen, and activation-induced intracellular cytokine and perforin expression in CD8 T cells was analysed by flow cytometry. RESULTS: Perforin-expressing HIV-1- and CMV-specific CD8 T cells can be quantified simultaneously. Within a patient, the frequency of such HIV-specific CD8 T cells in peripheral blood was lower than the frequency of the respective CMV-specific cells. The number of the perforin-expressing HIV-specific CD8 T cells inversely correlated with the peripheral blood CD4 T cell count. CONCLUSIONS: The differential fractions of perforin-expressing virus-specific CD8 T cells in HIV and CMV double infection might be caused by differences in priming and trafficking to or from replication sites. However, without knowing the underlying mechanism, the fraction of perforin-expressing HIV-specific CD8 T cells provides another surrogate marker for disease progression.