Expanded cytotoxic T-cell lymphocytes target the latent HIV reservoir

J Infect Dis. 2015 Jul 15;212(2):258-63. doi: 10.1093/infdis/jiv022. Epub 2015 Jan 13.

Abstract

Enhanced human immunodeficiency virus (HIV)-specific immunity may be required for HIV eradication. Administration of autologous, ex vivo expanded, virus-specific, cytotoxic T-lymphocytes derived from HIV-infected patients on suppressive antiretroviral therapy (HXTCs) are a powerful tool for proof-of-concept studies. Broadly specific, polyclonal HXTCs resulting from ex vivo expansion demonstrated improved control of autologous reservoir virus compared to bulk CD8(+) T cells in viral inhibition assays. Furthermore, patient-derived HXTCs were able to clear latently infected autologous resting CD4(+) T cells following exposure to the latency-reversing agent, vorinostat. HXTCs will be ideal reagents to administer with precise control in future in vivo studies in combination with latency-reversing agents.

Keywords: HIV T cells; HIV cure; HIV eradication; HIV immunology; adoptive T-cell therapy; ex vivo expanded T cells; latent reservoir; vorinostat.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Cells, Cultured
  • Coculture Techniques
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Hydroxamic Acids / therapeutic use
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • Vorinostat

Substances

  • Anti-HIV Agents
  • Hydroxamic Acids
  • Vorinostat