Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

It is currently widely accepted that immune activation in HIV-infected individuals leads to a severe loss of CD4＋ T cells and the progression to AIDS. However, the underlying mechanism of this immune activation remains unclear. Experimental data suggest that the activation of plasmacytoid dendritic cells （pDCs） by plasma viremia may play a critical role in HIV-induced immune activation. In this study, we found that the level of immune activation was higher in the late phase of SIVmac239 infection compared with chronic infection, which suggests that immune activation might be related to disease progression in SIVmac239-infected non-human primate models. Our work also showed that chloroquine could effectively inhibit the activation of pDCs in vitro and in vivo. However, chloroquine treatment of SIVmac239-infected macaques had no significant influence on the Cellular composition of peripheral blood in these animals.

The Influence of Age and Sex on the Cell Counts of Peripheral Blood Leukocyte Subpopulations in Chinese Rhesus Macaques

Non-human primates such as Chinese rhesus macaques are the favorable models for preclinical study of potential therapeutic drugs,vaccines and mechanisms of human diseases.Little is known about the normal levels of leukocyte subpopulations of Chinese rhesus macaques.To obtain these data,100 blood samples from Chinese rhesus macaques were collected.The normal range of major leukocyte subpopulations,such as T lymphocytes,B lymphocytes,monocytes,myeloid dendritic cells(mDCs)and plasmacytoid dendritic cells(pDCs),were quantitatively analyzed by flow cytometry through BD trucount tubes.The influence of age and sex on the cell counts of leukocyte subpopulations was analyzed.The counts of CD3^(+)T cells,CD3+CD4^(+)T cells,CD3+CD8^(+)T cells and B cells decreased with age,but those of monocytes,mDCs and pDCs had no significant correlation with age.Significant differences existed in the cell counts of most leukocyte subpopulations between the male and female groups except pDCs.Furthermore the values of the females were higher than those of the males.The study provided basic information about the leukocyte subpopulations of Chinese rhesus macaques,and it may be valuable for immunobiological study of Chinese rhesus macaques.

Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

Dendritic cells （DCs） play a pivotal role in linking the innate immunity and acquired immunity in responses to pathogen. Non-human primates such as Chinese Rhesus Macaque （CRM） are the favorable models for preclinical study of potential therapeutic drugs, vaccines and mechanisms of human diseases. However, the phenotypical characterization of monocyte-derived dendritic cells （MDDCs） from CRM has not been elucidated. Monocytes from CRM were cultured with GM-CSF and IL-4 in RPMI-1640. Six days later, these cells were differentiated with typical dendritical morphology. CDllc and DC-SIGN were highly expressed. The immature MDDCs expressed the low levels of CD25, CD80, CD83, moderate CD40, CD86, and high MHC. After stimulation, the mature MDDCs increased expression of mature molecules CD25 and CD83, co-stimulatory molecules such as CD80, CD86 and CD40, and kept a high level of MHC. The capacity of endocytosis decreased with maturation. The mature MDDCs have strong ability of inducing allogeneic T cell proliferation and producing IL-12. In conclusion, we have characterized the phenotype and ultimate function of MDDCs from CRM for the first time.