摘要
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-l-specific CTL frequency and HIV-1 epitope-specific, interferon-y （IFN-y）-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-y-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-l-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-l-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.
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-l-specific CTL frequency and HIV-1 epitope-specific, interferon-y （IFN-y）-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-y-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-l-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-l-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.
基金
This work was supported by the grants from the National Key Basic Research Program of China (No. 2001CB51003) and the National Natural Science Foundation of China (No. 30228025).
