Phenotypic and functional profile of IFN-α-differentiated dendritic cells (IFN-DCs) from HIV-infected individuals

ABSTRACT

Dendritic cell (DC)-based immunotherapy is a promising strategy for the treatment of HIV-infected individuals. Different from the conventional protocol for DC differentiation based on the cytokine IL-4 (IL4-DCs), several studies have suggested obtaining DCs by culturing monocytes with type I IFN (IFN-α) to yield IFN-DCs, as performed in cancer therapy. To evaluate the phenotypic and functional characteristics, monocytes from HIV-infected subjects were differentiated into IFN-DCs or IL4-DCs, pulsed with chemically inactivated HIV and stimulated with pro-inflammatory cytokines. A comparative analysis between both types of monocyte-derived DCs (MoDCs) showed that immature IFN-DCs were phenotypically distinct from immature IL4-DCs at the baseline of differentiation, presenting a pre-activated profile. From the functional profile, we determined that IFN-DCs were capable of producing the cytokine IL-12 p70 and of inducing the production of IFN-γ by CD4 + T lymphocytes but not by TCD8+ lymphocytes. Our results suggest that IFN-DCs derived from HIV-infected individuals are able to recognize and present viral antigens to induce TCD4+ cellular immunity to HIV.

KEYWORDS:

• dendritic cells
• type I interferon
• HIV
• immunotherapy

Acknowledgments

The authors thank all study participants, Dr Sadia Samer for critical comments, and Dr Alexandre de Almeida, Dr Jorge Casseb and Mariana Monteiro for patient recruitment.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Authors’ contributions

BTS and TMO conceived and designed the experiments and drafted the manuscript; BTS, DSR, LTS and NTR performed the experiments, data analysis and interpretation, and TMO and ADJS provided intellectual guidance during the project.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study has been financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001; and by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) - processes number 2012/02015-2 and 2017/22131-0.