Allogeneic sensitization is more effective than xenogeneic sensitization in eliciting gal-mediated skin graft rejection

The generation of Gal knockout (KO) pigs is likely to be an important advance in xenotransplantation. However, recent reports suggesting that expression of Gal may not be completely eliminated raise the possibility of a continuing anti-Gal immune response. The authors used a Gal-mismatched skin graft model to study cell-mediated anti-Gal rejection. Gal KO mice on a BALB/c or C57BL/6 background were sensitized with allogeneic or xenogeneic (rat) Gal-positive skin grafts and underwent transplantation with a secondary skin graft solely mismatched for Gal 21 days later. Most allograft-sensitized recipients rejected the secondary graft (n=26 [96%]) compared with less than half of xenograft-sensitized recipients (n=25 [44%]). An immunoglobulin (Ig) M response was detected in some xenograft-sensitized but not allograft-sensitized recipients. No recipients developed detectable anti-Gal IgG. The authors' findings contrast with previous reports that xenografts are more potent than allografts in eliciting an anti-Gal response and suggest that a predominantly cell-mediated response can mediate rejection.