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.
Zhang
Zheng
Z
Research Center of Biological Therapy, PLA 302 Hospital, Beijing, China.
Zhao
Qing-xia
QX
Fu
Jun-liang
JL
Yao
Jin-xia
JX
He
Yun
Y
Jin
Lei
L
Wang
Fu-sheng
FS
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D000939:Epitopes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014766:Viremia / Q000188:drug therapy*
D000939:Epitopes