Lentivirally Transduced Recipient-derived Dendritic Cells Serve to Ex Vivo Expand Functional FcRγ-sufficient Double-negative Regulatory T Cells. Mol Ther 2007 Apr;15(4):818-824
Date
04/01/2007Pubmed ID
28192704DOI
10.1038/sj.mt.6300082Scopus ID
2-s2.0-33947264163 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
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.
