PD-1, IL-10, IFN-γ and IL-12 form a network to regulate HIV-1-specific CD4 T Cell and antigen-presenting cell function

Abstract

Background PD-1 and IL-10 blockade can restore antigen-specific T cell functions in chronic infections and cancer. However, not all subjects respond to inhibition of either pathway, the potential differences in functions restored by these interventions are unknown, and mechanistic interactions between these pathways are poorly understood. Methods We investigated 45 subjects with HIV-1 infection with different disease status. We used CFSE assays to measure proliferation of HIV-1-specific CD4 T cells and Luminex arrays to analyze IFN-g(Th1), IL-2(Th0), IL-13(Th2) and IL-12 secretion in supernatants of CD8-depleted PBMC stimulated for 48h with Gag peptide pools in the presence of isotype control antibody, anti-PD-L1 and/or anti-IL-10Ra, anti-IFN-g or anti-IL-12. We used flow cytometry to evaluate the role of IFN-g in regulating PD-L1, HLA-DR, HLA-ABC and CD86 expression by monocytes.