Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals

Nat Med. 2006 Oct;12(10):1160-6. doi: 10.1038/nm1475. Epub 2006 Sep 24.

Abstract

Immunocompromised individuals are at high risk for life-threatening diseases, especially those caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus. Conventional therapeutics are primarily active only against CMV, and resistance is frequent. Adoptive transfer of polyclonal cytotoxic T lymphocytes (CTLs) specific for CMV or EBV seems promising, but it is unclear whether this strategy can be extended to adenovirus, which comprises many serotypes. In addition, the preparation of a specific CTL line for each virus in every eligible individual would be impractical. Here we describe genetic modification of antigen-presenting cell lines to facilitate the production of CD4(+) and CD8(+) T lymphocytes specific for CMV, EBV and several serotypes of adenovirus from a single cell culture. When administered to immunocompromised individuals, the single T lymphocyte line expands into multiple discrete virus-specific populations that supply clinically measurable antiviral activity. Monoculture-derived multispecific CTL infusion could provide a safe and efficient means to restore virus-specific immunity in the immunocompromised host.

Publication types

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

MeSH terms

  • Adenoviridae / metabolism
  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Culture Techniques / methods*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Cytomegalovirus / metabolism
  • Female
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Immune System Diseases / blood*
  • Immune System Diseases / therapy*
  • Immunophenotyping
  • Male
  • Middle Aged
  • T-Lymphocytes / metabolism