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Forum on Immunopathological Diseases and Therapeutics

ISSN Print: 2151-8017
ISSN Online: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.2016014160
pages 67-77

Programming T cell Killers for an HIV Cure: Teach the New Dogs New Tricks and Let the Sleeping Dogs Lie

Kellie N. Smith
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA; Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA
Robbie B. Mailliard
Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA
Charles R. Rinaldo
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Infectious Diseases and Microbiology, Pathology, University of Pittsburgh, Pittsburgh, PA

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 naive 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 naive T cells and will necessitate "teaching new dogs new tricks" while avoiding activation of potentially dysfunctional endogenous memory CTLs (letting the sleeping dogs lie).