Dendritic Cells Restore CD8 T Cell Reactivity to Autologous HIV-1

Recall T cell responses to HIV-1 antigens are used as a surrogate for endogenous cellular immune responses generated during infection. Current methods of identifying antigen-specific T cell reactivity in HIV-1 infection use bulk peripheral bloodmono-nuclear cells (PBMC) yet ignore professional antigen-presenting cells (APC) that could reveal otherwise hidden responses. In the present study, peptides representing autologous variants of major histocompatibility complex (MHC) class I-restricted epitopes fromHIV-1 Gag and Env were used as antigens in gamma interferon (IFN-) enzyme-linked immunosorbent spot (ELISpot) and polyfunctional cytokine assays. Here we show that dendritic cells (DC) enhanced T cell reactivity at all stages of disease progres-sion but specifically restored T cell reactivity after combination antiretroviral therapy (cART) to early infection levels. Type 1 cytokine secretion was also enhanced by DC and was most apparent late post-cART.We additionally show that DC reveal poly-functional T cell responses after many years of treatment, when potential immunotherapies would be implemented. These data underscore the potential efficacy of DC immunotherapy that aims to awaken a dormant, autologous, HIV-1-specific CD8 T cell response. IMPORTANCE Assessment of endogenous HIV-1-specific T cell responses is critical for generating immunotherapies for subjects on cART. Cur-rent assays ignore the ability of dendritic cells to reveal these responses andmay therefore underestimate the breadth andmagni