Survival of islet isografts despite cytotoxicity against pancreatic islets measured in vitro.
In this study the in vivo relevance of spleen cell anti-islet cytotoxicity measured in vitro was examined by transplantation of 1,200 syngeneic islets into the spleen of rats receiving 0.5 ml complete Freund's adjuvant (CFA) 24 h before 25 mg/kg body weight streptozotocin (STZ) was given. Control rats receiving CFA or STZ alone remained normoglycaemic whereas 12 out of 21 CFA/STZ-treated rats developed a severe hyperglycaemia after three combined treatments. After the first and second combined treatment splenocytes showed a significant cytotoxicity (p less than 0.01) against syngeneic islets measured by 51Cr-release. This cytotoxicity was not detectable after the third combined treatment. The CFA/STZ-induced diabetes with a residual pancreatic insulin content of only 5% was permanently reversed by intrasplenic islet isografts, but, surprisingly, syngeneic islets survived too, if transplanted at the time when an anti-islet cytotoxicity was measured in vitro. From our results we conclude that the polyclonal activation by complete Freund's adjuvant potentiates the beta cell-toxic effect of a low dose of streptozotocin and induced a transient splenocyte-mediated anti-islet cytotoxicity not recurrent after islet transplantation. Furthermore, our findings reveal a discrepancy between organ-specific immune reactions measured in vitro and those affecting the beta cells in vivo.
Ziegler
B
B
Central Institute of Diabetes, Gerhardt Katsch, Karlsburg/GDR.
Köhler
E
E
Klöting
I
I
Besch
W
W
Ziegler
M
M
D000818:Animals; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005620:Freund's Adjuvant; D005947:Glucose / Q000378:metabolism; D006085:Graft Survival; D006943:Hyperglycemia / Q000601:surgery; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013311:Streptozocin; D014185:Transplantation, Isogeneic
D007328:Insulin; D013311:Streptozocin; D005620:Freund's Adjuvant; D005947:Glucose