This dissertation was composed of three correspondingly independent parts.
Phenotype and function of monocytes-derived dendritic cells (MDDC) from Chinese
rhesus macaques, dynamic and functional changes of blood myeloid and
plasmacytoid dendritic cells during SIVmac239 infection in Chinese Rhesus
macaques and effect of SIVmac239 infection on apoptosis and immunophenotype of
blood CD1c+ myeloid and plasmacytoid dendritic cells in Chinese Rhesus
Macaques.
Non-human primates are abroad used in AIDS researches as animal models for
preclinical study of potential therapeutic drugs, vaccines and mechanisms. Compared
with Indian rhesus macaques, SIV infected Chinese rhesus macaques are more
suitable for AIDS researches. We first cultured and characterized MDDC from
Chinese rhesus macaques. Monocytes were cultured in RPMI-1640 with GM-CSF
and IL-4 for 6 days and stimulated to mature with a cocktail of IL-1β, PGE2, LPS
and TNF-α. Mature MDDC increased expression of co-stimulatory molecules and
CD83, and acquired a strong ability of making the allogeneic T cell proliferation and
producing high level of IL-12. This study is a part work of DC vaccine research.
Our lab has established the SIVmac239 infected Chinese rhesus macaques’
animal models. Depended on this model, we detected the dynamic,
英文摘要
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immunophenotypic and functional changes of blood DC subsets. DC played a crucial
role in inducing and regulating anti-HIV immune responses. Defects in the number
and functions of both myeloid DC and plasmacytoid DC have been observed in the
course of HIV infection and during disease progression. In our study, the number of
both mDC and pDC strongly fluctuated but no significantly change during acute and
chronic phases of SIVmac239 infection. The return of DC number in chronic phases
may lead to a slow progression. Both the concentration of poly (I:C) induced IL-12
and HSV-1 induced IFN-α significantly increased in the acute phase of infection
while returned to a normal levels at the chronic phase of infection. The peak of
IFN-α emergence was earlier than that of IL-12, and it had a significantly positive
correlation with IL-12, which indicated IFN-α may initiate the immune activation.
We also found only the concentration of IFN-α positively correlated with CD4+ T
cells counts, while negatively correlated with viral load. Our findings indicate that
high levels of IFN-α in early stage of infection may contribute to the effective
control of virus replication and the normal level of IFN-α in chronic infection may
help Chinese rhesus macaques resist the disease progression.
Followed, we studied the influence of SIV on the status of DC subsets during
acute phases of infection. We found the pDC were more prone to apoptosis after
infection which may be due to their high expressions of CD4 and CCR5. Both mDC
and pDC decreased CD4 expression while enhanced CCR5 expression. This trend of
pDC was more obviously because the mDC were low expressions of CD4 and CCR5.
Interestingly, the plasma viral load was negatively correlated with CD4 MFI of pDC
while positively correlated with CCR5 MFI of pDC. During this period, both mDC
and pDC were active to enhance expressions of co-stimulatory molecules,
accompanied with increase of CCR7. Either CD80 or CD86 expressed on mDC and
pDC was positively correlated with plasma viral load. The activation of DC is
benefitial to control the replication of SIV and to resist the disease progression.
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