title: Effects of acute cytomegalovirus infection on rat islet allograft survival.
abstract: Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic  rats received an allogenic islet graft in combination with either an acute CMV infection or control infection. A third group received ganciclovir treatment in addition to the CMV infection. Graft function was assessed by measuring basal blood glucose levels. After sacrifice, the islet grafts  were retrieved for analysis of infection and leukocyte infiltration. CMV-infected recipients demonstrated accelerated islet graft failure compared to noninfected controls. CMV infection of the graft was only observed prior to complete graft failure. Quantification of the leukocyte infiltration  demonstrated increased CD8(+) T-cell and NK cell infiltration in the CMV-infected grafts compared to the controls. This suggests that CMV infection accelerates immune-mediated graft destruction. Antiviral ganciclovir treatment did not prevent accelerated graft failure, despite effectively  decreasing the grade of infection. Our data confirm the recently published CITR data, which state that CMV is an independent risk factor for failure of islet grafts. Also, our data demonstrate that new approaches for preventing virus-induced islet allograft failure may be required.
authors.affiliation: Department of Pathology and Medical Biology, Division of Medical Biology, Section Immunoendocrinology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. m.j.smelt@med.umcg.nl
authors.forename: M J
authors.initials: MJ
authors.lastname: Smelt
authors.forename: B J
authors.initials: BJ
authors.lastname: de Haan
authors.forename: M M
authors.initials: MM
authors.lastname: Faas
authors.forename: B N
authors.initials: BN
authors.lastname: Melgert
authors.forename: A
authors.initials: A
authors.lastname: de Haan
authors.forename: P
authors.initials: P
authors.lastname: de Vos
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology*; D015774:Ganciclovir / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007109:Immunity / Q000187:drug effects; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D012469:Salivary Glands / Q000187:drug effects / Q000821:virology; D014184:Transplantation, Homologous
chemical_list: D000998:Antiviral Agents; D001786:Blood Glucose; D015774:Ganciclovir