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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Seino
K
K
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Kayagaki
N
N
Tsukada
N
N
Fukao
K
K
Yagita
H
H
Okumura
K
K
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D053222:Fas Ligand Protein; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007940:Leukemia L5178 / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014162:Transfection; D014185:Transplantation, Isogeneic; D019014:fas Receptor / Q000502:physiology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019014:fas Receptor