Gene combination transfer to block autoimmune damage in transplanted islets of Langerhans.
Islet transplantation therapy would be applicable to a wider range of diabetic patients if donor islet acceptance and protection were possible without systemic immunosuppression of the recipient. To this aim, gene transfer to isolated donor islets ex vivo is one method that has shown promise. This study examines the combined effect of selected immunomodulatory and anti-inflammatory genes known to extend the functional viability of pancreatic islet grafts in an autoimmune system. These genes, indoleamine 2,3-dioxygenase (IDO), manganese superoxide dismutase (MnSOD), and interleukin (IL)-1 receptor antagonist protein (IRAP), were transferred to isolated NOD donor islets ex vivo then transplanted to NODscid recipients and evaluated in vivo after diabetogenic T-cell challenge. The length of time the recipient remained euglycemic was used to measure the ability of the transgenes to protect the graft from autoimmune destruction. Although the results of these cotransfections gave little evidence of a synergistic relationship, they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenic T cells.
Bertera
Suzanne
S
Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA. subst5@pitt.edu
Alexander
Angela M
AM
Crawford
Megan L
ML
Papworth
Glenn
G
Watkins
Simon C
SC
Robbins
Paul D
PD
Trucco
Massimo
M
D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000473:pathology; D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053590:Interleukin 1 Receptor Antagonist Protein; D007515:Islets of Langerhans / Q000473:pathology* / Q000503:physiopathology; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012795:Sialoglycoproteins / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D013997:Time Factors; D014366:Tryptophan Oxygenase / Q000235:genetics*
D001786:Blood Glucose; C507764:Il1rn protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D014366:Tryptophan Oxygenase; D013482:Superoxide Dismutase