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  

作　　者：ZHANG Zheng ZHAO Qing-xia FU Jun-liang YAO Jin-xia HE Yun JIN Lei WANG Fu-sheng 

机构地区：[1]Research Center of Biological Therapy, PLA 302 Hospital, Beijing100039, China [2]Department of Infectious Diseases, Zhengzhou Sixth Hospital,Zhengzhou 450054, China

出　　处：《Chinese Medical Journal》2006年第23期1949-1957,共9页中华医学杂志（英文版）

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).

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.

关 键 词：cytotoxic T lymphocyte dendritic cells human immunodeficiency virus CHILD 

分 类 号：R512.91[医药卫生—内科学]