Characteristics of HIV-1-specific CD8 T-cell responses and their role in loss of viremia in children chronically infected with HIV-1 undergoing highly active antiretroviral therapy.

BACKGROUND: Few studies have examined the properties of human immunodeficiency virus type 1 (HIV-1) epitope-specific cytotoxic T lymphocyte (CTL) responses in children. To address this issue, we characterized epitope-specific CTL responses and analyzed the determinants that may affect CTL responses before and after highly active antiretroviral therapy (HAART) in children with HIV-1 infection. METHODS: A total of 22 HIV-1-infected children and 23 uninfected healthy children as control were enrolled in the study. Circulating CD4 T cells and HIV-1 RNA load in plasma were routinely measured. Peripheral HIV-1-specific CTL frequency and HIV-1 epitope-specific, interferon-gamma (IFN-gamma)-producing T lymphocytes were measured using tetramer staining and enzyme-linked immunospot (ELISPOT) assay, respectively. Circulating dendritic cell (DC) subsets were monitored with FACS analysis. RESULTS: More than 80% of the children with HIV-1 infection exhibited a positive HIV-1-epitope-specific CTL response at baseline, but HIV-specific CTLs and IFN-gamma-producing lymphocytes decreased in patients who responded to HAART in comparison with non-responders and HAART-naive children. The duration of virus suppression resulted from HAART was inversely correlated with CTL frequency. While in HAART-naive children, HIV-1-specific CTL frequency was positively correlated with myeloid DC (mDC) frequency, although the cause and effect relationship between the DCs and CTLs remains unknown. CONCLUSIONS: HIV-1-epitope-specific CTL responses are dependent on antigenic stimulation. The impaired DC subsets in blood might result in a defect in DC-mediated T cell responses. These findings may provide insight into understanding the factors and related mechanisms that influence the outcome of HIV-1 carriers to HAART or future antiviral therapies.

[The characterization of regulatory T cells in peripheral blood of HBV-infected patients].

OBJECTIVE: CD4(+)CD25(high) regulatory T cells (Treg) have been shown to play an important role in maintaining peripheral tolerance against self and foreign antigens, and in suppressing T cell immune response. Our aim was to characterize circulating Treg in HBV-infected patients. METHODS: Treg in peripheral blood from 72 chronic hepatitis B (CHB) patients, 16 acute hepatitis B (AHB) patients and 32 healthy subjects were quantitatively analyzed using flow cytometry. Serum HBV markers were evaluated for each subject. HBV-DNA levels were measured using real-time RT-PCR. RESULTS: CHB patients presented a higher fraction of circulating Treg (3.9% +/- 1.4%) than those in AHB patients (3.1% +/- 0.9%) (P < 0.05), but were similar to healthy controls (3.5% +/- 0.7%). CHB patients with greater than 10(7) copies/ml of serum HBV DNA loads had a higher frequency (4.5% +/- 1.9%) of circulating Treg than health controls (P < 0.01) and the patients with less than 10(7) copies/ml of serum viral loads (3.4% +/- 0.7%). A correlation was found between circulating Treg and HBV DNA level (r = 0.32, P < 0.01). Furthermore, Treg was more frequent in convalescent phase (6.0% +/- 1.7%) than in early acute phase (3.0% +/- 0.6%). CONCLUSION: Increased peripheral Treg is found to be associated with HBV replication in chronic hepatitis B. In acute HBV infection, Treg is less frequent in early phase. The related mechanisms is under further investigation.

[Identification of circulating plasmacytoid dendritic cells in chronic HBV-infected patients].

OBJECTIVE: To investigate the features of circulating plasmacytoid dendritic cells (pDCs) in patients with chronic hepatitis B for a better understanding of the immunopathogenesis of HBV infection. METHODS: Fresh blood samples were collected from 20 patients with chronic hepatitis B (CHB) and from 15 healthy individuals who served as controls. pDCs were isolated from peripheral blood mononuclear cells (PBMCs) using immunomagnetic assay and detected by flow cytometry. Fresh PBMCs and isolated pDCs were stimulated in vitro using CpG ODN2216. The supernatants were measured for IFNa production using ELISA. RESULTS: The peripheral pDCs frequency in CHB patients (0.192%+/-0.110%) was markedly lower than that in the healthy controls (0.287%+/-0.142%). After being pulsed with CpG ODN2216, the isolated pDCs produced lower levels of IFNa and expressed lower levels of CD80 and CD40 in the CHB patients when compared to those of the healthy controls. The level of IFNa was (972.6+/-705.5) pg/ml in the patients and (3 142.9+/-1 292.2) pg/ml in the controls. Moreover, the pDCs frequency was reversely correlated with serum ALT levels in these HBV infected patients. CONCLUSION: The reduced number and impaired function of circulating pDCs in patients with CHB may be related to their disease progression.