title: Susceptibility of human pancreatic β cells for cytomegalovirus infection and the effects on cellular immunogenicity.
abstract: OBJECTIVE
  Human cytomegalovirus (HCMV) infection has been suggested to be a causal factor in the development of type 1 diabetes, posttransplantation diabetes, and the failure of islet allografts. This effect of CMV has been interpreted as an indirect effect on the immune system rather than direct infection-induced cell death. In the present study, we investigated (i) the susceptibility of β cells to HCMV infection, (ii) regulation of immune cell-activating ligands, (iii) release of proinflammatory cytokines, and (iv) the effects on peripheral blood mononuclear cell (PBMC) activation.
  
  
  METHODS
  CM insulinoma cells and primary β cells were HCMV-infected in vitro using a laboratory and a clinical HCMV strain. The susceptibility to infection was measured by the expression of viral genes and proteins. Furthermore, expression levels of Major Histocompatibility Complex I, Intracellular Adhesion Molecule-1, and Lymphocyte Function Associated Antigen-3 and the release of proinflammatory cytokines were determined. In addition, PBMC activation to HCMV-infected β cells was determined.
  
  
  RESULTS
  β Cells were susceptible to HCMV infection. Moreover, the infection increased the cellular immunogenicity, as demonstrated by an increased MHC I and ICAM-1 expression and an increased proinflammatory cytokine release. Human cytomegalovirus-infected CM cells potently activated PBMCs. The infection-induced effects were dependent on both viral "sensing" and viral replication.
  
  
  CONCLUSIONS
  In vivo β-cell HCMV infection and infection-enhanced cellular immunogenicity may have important consequences for native or transplanted β-cell survival.
authors.affiliation: Section of Transplantation Biology and Immunoendocrinology, Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands. m.j.smelt@med.umcg.nl
authors.forename: Maaike J
authors.initials: MJ
authors.lastname: Smelt
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Faas
authors.forename: Bart J
authors.initials: BJ
authors.lastname: de Haan
authors.forename: Christina
authors.initials: C
authors.lastname: Draijer
authors.forename: Greg C G
authors.initials: GC
authors.lastname: Hugenholtz
authors.forename: Aalzen
authors.initials: A
authors.lastname: de Haan
authors.forename: Marten A
authors.initials: MA
authors.lastname: Engelse
authors.forename: Eelco J P
authors.initials: EJ
authors.lastname: de Koning
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
mesh_terms: D018968:CD58 Antigens / Q000276:immunology / Q000378:metabolism; D002102:Cadaver; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000821:virology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000276:immunology*; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007340:Insulinoma / Q000276:immunology / Q000473:pathology / Q000821:virology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D018968:CD58 Antigens; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins; D018799:Intercellular Adhesion Molecule-1