Identification of the tetraspanin CD82 as a new barrier to xenotransplantation.

ABSTRACT: Significant immunological obstacles are to be negotiated before xenotransplantation becomes a clinical reality. An initial rejection of transplanted vascularized xenograft is attributed to Gal?1,3Gal?1,4GlcNAc-R (Gal?1,3-Gal)-dependent and -independent mechanisms. Hitherto, no receptor molecule has been identified that could account for Gal?1,3-Gal-independent rejection. In this study, we identify the tetraspanin CD82 as a receptor molecule for the Gal?1,3-Gal-independent mechanism. We demonstrate that, in contrast to human undifferentiated myeloid cell lines, differentiated cell lines are capable of recognizing xenogeneic porcine aortic endothelial cells in a calcium-dependent manner. Transcriptome-wide analysis to identify the differentially expressed transcripts in these cells revealed that the most likely candidate of the Gal?1,3-Gal-independent recognition moiety is the tetraspanin CD82. Abs to CD82 inhibited the calcium response and the subsequent activation invoked by xenogeneic encounter. Our data identify CD82 on innate immune cells as a major "xenogenicity sensor" and open new avenues of intervention to making xenotransplantation a clinical reality.

SUBMITTER: Saleh SM 

PROVIDER: S-EPMC3748337 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature