title: Programming T cell Killers for an HIV Cure: Teach the New Dogs New Tricks and Let the Sleeping Dogs Lie.
abstract: Despite the success of combination antiretroviral therapy (cART), a latent viral reservoir persists in HIV-1-infected persons. Unfortunately, endogenous cytotoxic T lymphocytes (CTLs) are unable to control viral rebound when patients are removed from cART. A "kick and kill" strategy has been proposed to eradicate this reservoir, whereby infected T cells are induced to express viral proteins via latency-inducing drugs followed by their elimination by CTLs. It has yet to be determined if stimulation of existing HIV-1-specific CTL will be sufficient, or if new CTLs should be primed from naïve T cells. In this review, we propose that dendritic cells (DCs), the most potent antigen presenting cells, act as dog trainers and can induce T cells (the dogs) to do magnificent tricks. We propose the hypothesis that an HIV-1 cure will require targeting of naïve T cells and will necessitate "teaching new dogs new tricks" while avoiding activation of potentially dysfunctional endogenous memory CTLs (letting the sleeping dogs lie).
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA; Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Kellie N
authors.initials: KN
authors.lastname: Smith
authors.affiliation: Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Robbie B
authors.initials: RB
authors.lastname: Mailliard
authors.affiliation: Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA; Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
keywords: CTL; HIV-1; dendritic cells; immunotherapy