title: Differential Impact of Chronic Hyperglycemia on Humoral Versus Cellular Primary Alloimmunity.
abstract: Diabetes is prevalent among solid organ transplant recipients and is universal among islet transplant recipients. Whereas diabetes is often considered to result in an immune-compromised state, the impact of chronic hyperglycemia on host alloimmunity is not clear. Potential immune-modifying effects of obesity, autoimmunity, or diabetogenic agents like streptozotocin may confound understanding alloimmunity in experimental models of diabetes. Therefore, we sought to determine the role of chronic hyperglycemia due to insulinopenia on alloimmunity using the nonautoimmune, spontaneously diabetic H-2b-expressing C57BL/6Ins2Akitamice (Akita). Akita mice harbor a mutatedIns2allele that dominantly suppresses insulin secretion, resulting in lifelong diabetes. We used BALB/c donors (H-2d) to assess alloimmunization and islet transplantation outcomes in Akita recipients. Surprisingly, chronic hyperglycemia had little effect on primary T-cell reactivity after alloimmunization. Moreover, Akita mice readily rejected islet allografts, and chronic hyperglycemia had no impact on the magnitude or quality of intragraft T-cell responses. In contrast, allospecific IgM and IgG were significantly decreased in Akita mice after alloimmunization. Thus, whereas diabetes influences host immune defense, hyperglycemia itself does not cause generalized alloimmune impairment. Our data suggest that immune compromise in diabetes due to hyperglycemia may not apply to cellular rejection of transplants.
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Bishop
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Nelsen
authors.affiliation: Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: K Scott
authors.initials: KS
authors.lastname: Beard
authors.affiliation: Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Coulombe
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO ronald.gill@ucdenver.edu.|Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Gill
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000276:immunology* / Q000601:surgery; D006084:Graft Rejection / Q000276:immunology*; D006943:Hyperglycemia / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007328:Insulin / Q000235:genetics; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: C561967:Ins2 protein, mouse; D007328:Insulin