title: Allograft-specific cytokine profiles associate with clinical outcome after islet cell transplantation.
abstract: Islet cell transplantation can cure type 1 diabetes, but allograft rejection and recurrent autoimmunity may contribute to decreasing insulin independence over time. In this study we report the association of allograft-specific proliferative and cytokine profiles with clinical outcome. Peripheral blood mononuclear cells were obtained of 20 islet recipients. Cytokine values in mixed lymphocyte cultures (MLC) were determined using stimulator cells with graft-specific HLA class II. Qualitative and quantitative cytokine profiles were determined before and after islet transplantation, blinded from clinical outcome. Cytotoxic T Lymphocyte precursor (CTLp) assays were performed to determine HLA class I alloreactivity. Allograft-specific cytokine profiles were skewed toward a Th2 or regulatory (Treg) phenotype after transplantation in insulin-independent, but not in insulin-requiring recipients. IFNgamma/IL10 ratio and MLC proliferation decreased after transplantation in insulin-independent recipients (p = 0.006 and p = 0.01, respectively). Production of the Treg cytokine IL10 inversely correlated with proliferation in alloreactive MLC (p = 0.008) and CTLp (p = 0.005). Production of IL10 combined with low-MLC reactivity associated significantly with insulin independence. The significant correlation between allograft-specific cytokine profiles and clinical outcome may reflect the induction of immune regulation in successfully transplanted recipients. Islet donor-specific IL10 production correlates with low alloreactivity and superior islet function.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: V A L
authors.initials: VA
authors.lastname: Huurman
authors.forename: J H L
authors.initials: JH
authors.lastname: Velthuis
authors.forename: R
authors.initials: R
authors.lastname: Hilbrands
authors.forename: T I M
authors.initials: TI
authors.lastname: Tree
authors.forename: P
authors.initials: P
authors.lastname: Gillard
authors.forename: P M W
authors.initials: PM
authors.lastname: van der Meer-Prins
authors.forename: G
authors.initials: G
authors.lastname: Duinkerken
authors.forename: G G M
authors.initials: GG
authors.lastname: Pinkse
authors.forename: B
authors.initials: B
authors.lastname: Keymeulen
authors.forename: D L
authors.initials: DL
authors.lastname: Roelen
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
authors.forename: D G
authors.initials: DG
authors.lastname: Pipeleers
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
mesh_terms: D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000628:therapy; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation; D007959:Lymphocyte Culture Test, Mixed; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D016207:Cytokines