Induction of donor-specific unresponsiveness by intrathymic islet transplantation.
The application of isolated pancreatic islet transplantation for treatment of diabetes mellitus has been hampered by the vulnerability of islet allografts to immunologic rejection. Rat islet allografts that were transplanted into the thymus of recipients treated with a single injection of anti-lymphocyte serum survived indefinitely. A state of donor-specific unresponsiveness was achieved that permitted survival of a second donor strain islet allograft transplanted to an extrathymic site. Maturation of T cell precursors in a thymic microenvironment that is harboring foreign alloantigen may induce the selective unresponsiveness. This model provides an approach for pancreatic islet transplantation and a potential strategy for specific modification of the peripheral immune repertoire.
Posselt
A M
AM
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104.
Barker
C F
CF
Tomaszewski
J E
JE
Markmann
J F
JF
Choti
M A
MA
Naji
A
A
D000818:Animals; D000961:Antilymphocyte Serum; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006082:Graft Enhancement, Immunologic; D007108:Immune Tolerance; D016381:Islets of Langerhans Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000601:surgery; D016042:Transplantation, Heterotopic
D000961:Antilymphocyte Serum; D001786:Blood Glucose