Protection of islet allografts transplanted together with Fas ligand expressing testicular allografts.
Fas ligand (FasL) is highly expressed in testicular tissues and thought to be responsible for protection from allograft rejection by inducing apoptosis of anti-graft activated T cells. FasL-expressing islets have been shown to induce a granulocyte-mediated inflammatory reaction. We investigated whether a graft can be protected from alloimmune responses by manipulating the Fas/FasL-system. We transplanted allogeneic islets under the kidney capsule of streptozotocin-induced diabetic mice together with testicular tissue. Significant prolongation of survival of C3H islet allograft was observed in C57BL/6 (B6) recipients transplanted with C3H testicular tissue, but not in those transplanted with C3H-gld testicular tissue expressing non-functional FasL. No significant prolongation was observed in B6-lpr recipients expressing non-functional Fas. Immunohistochemical staining of C3H testicular tissue in the composite graft showed a high expression of FasL, but not that of the C3H-gld testicular tissue. In situ terminal deoxynucleotidyl transferase-mediated dUDP-biotin catalysed DNA nick-end labelling (TUNEL) staining of a composite graft of C3H islet and testicular tissue in B6 recipients demonstrated extensive apoptosis of infiltrating mononuclear cells around the graft. The protective effect of C3H testicular tissue was abrogated when anti-FasL monoclonal antibody was administered i.p. postoperatively. Our results suggest that FasL-positive testicular allografts protect composite islet allografts and indicate that manipulation of Fas/FasL mediated apoptosis is a suitable strategy for controlling rejection of islet allografts.
Takeda
Y
Y
Department of Surgery II, Osaka University Medical School, Suita, Japan.
Gotoh
M
M
Dono
K
K
Nishihara
M
M
Grochowiecki
T
T
Kimura
F
F
Yoshida
T
T
Ohta
Y
Y
Ota
H
H
Ohzato
H
H
Umeshita
K
K
Takeda
T
T
Matsuura
N
N
Sakon
M
M
Kayagaki
N
N
Yagita
H
H
Okumura
K
K
Miyasaka
M
M
Monden
M
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007668:Kidney / Q000737:chemistry / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013737:Testis / Q000737:chemistry / Q000378:metabolism* / Q000637:transplantation*; D014184:Transplantation, Homologous
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins