Lentivirally transduced recipient-derived dendritic cells serve to ex vivo expand functional FcRgamma-sufficient double-negative regulatory T cells. Mol Ther 2007 Apr;15(4):818-24
Date
02/01/2007Pubmed ID
17264854DOI
10.1038/sj.mt.6300082Scopus ID
2-s2.0-33947264163 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
alphabetaTCR(+)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 L(d) antigen (LV-L(d)), which is expressed by the donor graft but is allogeneic to the graft recipient. LV-L(d)-transduced mature DCs (mDCs) were able to expand effectively both FcRgamma(-/-) and FcRgamma(+/+) DN T cells. After expansion with LV-L(d)-transduced mDCs, only the FcRgamma(+/+) DN Treg cells maintained their ability to suppress CD8(+) T cells in vitro. In addition, adoptive transfer of the FcRgamma(+/+) ex vivo expanded DN Treg cells significantly prolonged the survival of L(d+) 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 FcRgamma(-/-) DN T cells can be expanded, they do not gain regulatory ability.
Author List
Thomson CW, Mossoba ME, Siatskas C, Chen W, Sung A, Medin JA, Zhang LAuthor
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDendritic Cells
Female
Genetic Vectors
Graft Survival
Humans
Immunotherapy, Adoptive
In Vitro Techniques
Lentivirus
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Receptors, IgG
Skin Transplantation
T-Lymphocytes, Regulatory
Transduction, Genetic