Lentivirally transduced recipient-derived dendritic cells serve to ex vivo expand functional FcRγ-sufficient double-negative regulatory T Cells

Christopher W. Thomson, Miriam E. Mossoba, Christopher Siatskas, Wenhao Chen, April Sung, Jeffrey A. Medin, Li Zhang

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

αβTCR+CD4-CD8- double-negative (DN) T regulatory (Treg) cells have recently been shown to suppress antigen-specific immune responses mediated by CD8+ and CD4+ T cells in mice and humans. In this study, we developed a system to expand DN Treg cells for transplantation therapy that exclusively uses recipient-derived immune cells and confers a high degree of safety as the protocol does not involve the direct injection of lentiviral vectors. Recipient-derived dendritic cells (DCs) were transduced with lentiviral vectors that express major histocompatibility complex class I Ld antigen (LV-Ld), which is expressed by the donor graft but is allogeneic to the graft recipient. LV-Ld-transduced mature DCs (mDCs) were able to expand effectively both FcRγ+/+ and FcRγ-/- DN T cells. After expansion with LV-Ld-transduced mDCs, only the FcRγ+/+ DN Treg cells maintained their ability to suppress CD8+ T cells in vitro. In addition, adoptive transfer of the FcRγ+/+ ex vivo expanded DN Treg cells significantly prolonged the survival of Ld+ skin grafts. This study is the first description of successful ex vivo expansion of antigen-specific DN Treg cells using genetically modified syngeneic DCs for adoptive immunotherapy and demonstrates that although FcRγ-/- DN T cells can be expanded, they do not gain regulatory ability.

Original languageEnglish (US)
Pages (from-to)818-824
Number of pages7
JournalMolecular Therapy
Volume15
Issue number4
DOIs
StatePublished - Apr 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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