Monocyte-derived dendritic cells from HIV-1 individuals show impaired functions that is not resolved by anti-retroviral therapy
Objectives: Monocyte-derived dendritic cells (mdDC) are powerful vaccine tools. As highly active anti-retroviral therapy fails to eradicate the virus, they are currently under consideration as adjuvants for therapeutic vaccination of HIV-infected individuals. In this study, we have investigated mdDC from HAART naïve and treated HIV-1 patients to determine whether they show normal DC features compatible with their use as therapeutic vaccines.
Methods: DC have been generated from monocytes of HIV-1+ naïve and ART-treated patients and healthy donors for 7 days in the presence of GM-CSF and IL-4. The phenotype has been analysed on immature and LPS-matured mdDC and their capacity to stimulate T cell evaluated by co-culturing mature mdDC with T cells. T cell proliferation has been measured by H3 thymidine incorporation after 5 days and the polarization of CD4+ T cells by IFNg/IL-4 production. Statistics have been performed using Mann-Whitney test.
Results: We did not see statistically significant in differences in mdDC between groups in the expression of membrane molecules although monocytes from HIV-1+ naïve patients frequently gave rise to a heterogenous CD1a+/CD1a- mdDC population compared to those from HIV-1+ HAART patients and HIV-1- healthy controls. There was no correlation of altered phenotype with low CD4+ T cell counts or high viral load. Co-stimulatory molecule expression was similar in all groups and there were no differences between HIV-1+ and HIV-1- individuals with regards to up-regulation upon maturation with LPS and sCD40L. Functionally, however, mdDC from both HIV+ naïve and HAART patients were severely impaired in their ability to induce T cell proliferation and to direct the differentiation of CD4 cells towards an IFNg-secreting Th-1 phenotype.
Conclusions: The results of this study suggest that these cells may not stimulate the appropriate immune response and indicate that the immunological properties of mdDC from each individual should be analysed before commencement of vaccination.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
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Monocyte-derived dendritic cells from HIV-1 individuals show impaired functions that is not resolved by anti-retroviral therapy.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: