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For Immunopathol Dis Therap. 2015;6(1-2):67-77. doi: 10.1615/ForumImmunDisTher.2016014160.

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

Author information

1
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA; Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA.
2
Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA.
3
Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA; 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 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).

KEYWORDS:

CTL; HIV-1; dendritic cells; immunotherapy

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