Distinct strategies are required to suppress antigen-specific responses to genetically modified keratinocytes and fibroblasts.

ABSTRACT: Keratinocytes and fibroblasts are potential targets of gene/cell therapy for genodermatoses. Immune elimination of genetically modified cells, however, presents a major impediment to effective therapy. Using ex vivo approaches to gene transfer, we have previously shown that expression of an antigen by either cell type in skin induces immune rejection of transplanted cells, although the nature of immune responses induced by these two cell types are distinct. In this study, we explore the efficacy of local immunosuppressive strategies to divert destructive immune responses from genetically modified fibroblast and keratinocytes. Expression of CTLA4Ig and, to a lesser extent, PDL1, by antigenic fibroblasts protected them from immune rejection resulting in long-term graft survival (>18 weeks).

SUBMITTER: Ghazizadeh S 

PROVIDER: S-EPMC3255584 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature