HIV-1 Infection and Maturation of Myeloid Dendritic Cells
HIV-1 Infection and Maturation of Myeloid Dendritic Cells
The functional and phenotypic maturation of myeloid dendritic cells (DCs), circulating and monocyte-derived, from subjects at different stages of HIV-1 infection was evaluated. The results showed that the capacity of circulating DCs was significantly impaired in subjects with CD4 T cell counts of <200/µL, correlated with the potential of CD40 ligand expression on CD4 T cells (R = 0.84; P = 0.002), and improved with successful antiretroviral therapy. However, the function and phenotype of monocyte-derived DCs generated by in vitro culture from subjects at any stage of HIV-1 infection were similar to those in uninfected healthy subjects. Our findings suggest that although the potential of myeloid DC precursors to achieve full maturation is preserved in subjects with late-stage HIV-1 infection, in vivo maturation of myeloid DCs was impaired in these subjects, which may be due to decreased potential of CD40 ligand expression on CD4 T cells. That myeloid DCs fail to achieve full maturation in vivo in late-stage HIV-1 infection may contribute to the failure to induce effective cellular immunity against HIV-1 and opportunistic pathogens.
Myeloid dendritic cells (DCs) are potent antigen-presenting cells and play critical roles in host defense. When these DCs mature, they not only link innate and adaptive immunity by presenting the processed antigens and costimulatory signals to activate specific T cells but also play an instructive role in adaptive immunity by regulating TH1-TH2 development. Therefore, mature DCs are essential for the development of protective T-cell immunity in vivo and have been used to elicit T-cell effector functions in vitro. After being pulsed with HIV-1 peptides or infected by virus vectors containing HIV genes, DCs exhibited strong immunostimulatory capacity to prime obvious HIV-1-specific cytotoxic T-lymphocyte responses. Actually, some DC-based immunotherapies have been developed to help control SIV or HIV-1 infection.
The potential of maturation of myeloid DC precursors from HIV-infected individuals is critical for the success of these immunotherapies. Some reports have addressed the influence of HIV-1 infection on the myeloid DCs in vivo and in vitro. Chehimi et al. and Barron et al. showed recently that the absolute numbers of blood myeloid DCs decreased significantly in HIV-1-infected individuals with active viral replication. In addition, some studies showed that the phenotypic maturation and functional capacity of myeloid DCs derived from monocytes of HIV-1-infected individuals were normal. However, information about the systemic analysis for the impact of different stages of HIV-1 infection on the myeloid DC maturation in vivo and in vitro is limited. In this study, we evaluated the functional capacity of circulating myeloid DCs to assess the DC maturation status in vivo and the functional and phenotypic maturation of monocyte-derived DCs (MDDCs) from in vitro culture to assess the potential of myeloid DC precursors to mature in subjects at different ranges of absolute CD4 T-cell counts. In addition, we assessed the recovery of myeloid DC function during successful antiretroviral therapy.
The functional and phenotypic maturation of myeloid dendritic cells (DCs), circulating and monocyte-derived, from subjects at different stages of HIV-1 infection was evaluated. The results showed that the capacity of circulating DCs was significantly impaired in subjects with CD4 T cell counts of <200/µL, correlated with the potential of CD40 ligand expression on CD4 T cells (R = 0.84; P = 0.002), and improved with successful antiretroviral therapy. However, the function and phenotype of monocyte-derived DCs generated by in vitro culture from subjects at any stage of HIV-1 infection were similar to those in uninfected healthy subjects. Our findings suggest that although the potential of myeloid DC precursors to achieve full maturation is preserved in subjects with late-stage HIV-1 infection, in vivo maturation of myeloid DCs was impaired in these subjects, which may be due to decreased potential of CD40 ligand expression on CD4 T cells. That myeloid DCs fail to achieve full maturation in vivo in late-stage HIV-1 infection may contribute to the failure to induce effective cellular immunity against HIV-1 and opportunistic pathogens.
Myeloid dendritic cells (DCs) are potent antigen-presenting cells and play critical roles in host defense. When these DCs mature, they not only link innate and adaptive immunity by presenting the processed antigens and costimulatory signals to activate specific T cells but also play an instructive role in adaptive immunity by regulating TH1-TH2 development. Therefore, mature DCs are essential for the development of protective T-cell immunity in vivo and have been used to elicit T-cell effector functions in vitro. After being pulsed with HIV-1 peptides or infected by virus vectors containing HIV genes, DCs exhibited strong immunostimulatory capacity to prime obvious HIV-1-specific cytotoxic T-lymphocyte responses. Actually, some DC-based immunotherapies have been developed to help control SIV or HIV-1 infection.
The potential of maturation of myeloid DC precursors from HIV-infected individuals is critical for the success of these immunotherapies. Some reports have addressed the influence of HIV-1 infection on the myeloid DCs in vivo and in vitro. Chehimi et al. and Barron et al. showed recently that the absolute numbers of blood myeloid DCs decreased significantly in HIV-1-infected individuals with active viral replication. In addition, some studies showed that the phenotypic maturation and functional capacity of myeloid DCs derived from monocytes of HIV-1-infected individuals were normal. However, information about the systemic analysis for the impact of different stages of HIV-1 infection on the myeloid DC maturation in vivo and in vitro is limited. In this study, we evaluated the functional capacity of circulating myeloid DCs to assess the DC maturation status in vivo and the functional and phenotypic maturation of monocyte-derived DCs (MDDCs) from in vitro culture to assess the potential of myeloid DC precursors to mature in subjects at different ranges of absolute CD4 T-cell counts. In addition, we assessed the recovery of myeloid DC function during successful antiretroviral therapy.
