Transplantation of CD95 ligand-expressing grafts: influence of transplantation site and difficulty in protecting allo- and xenografts.

Abstract

CD95 and its ligand (CD95L) have been implicated in the regulation of immune responses. Recently, it was reported that CD95L expression prevented rejection of allogeneic grafts transplanted under the kidney capsule. In contrast, we reported that enforced CD95L expression in subcutaneously grafted cells induced acute rejection even in the syngeneic or immunodeficient hosts. In this study, we investigated whether the CD95L-expressing cells could be protected from rejection when transplanted under the kidney capsule. CD95-negative cells (baby hamster kidney and L5178Y lymphoma cells) were transfected with CD95L cDNA to express functional CD95L. The cells were transplanted into skin or renal subcapsular space of immunocompetent or T cell-deficient nu/nu mice. The parental cells grew well in nu/nu or syngeneic mice but were rejected in allogeneic or xenogeneic immunocompetent mice. The CD95L transfectants were rejected when transplanted subcutaneously in all types of mice studied. However, when transplanted under the kidney capsule, they survived in nu/nu or syngeneic mice but were rejected in allogeneic or xenogeneic immunocompetent mice. These results imply that CD95L expression may not be sufficient to protect the grafts from rejection, and the survival of CD95L-bearing grafts is substantially influenced by the site of transplantation.