title: Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.
abstract: BACKGROUND
  Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA).
  
  
  OBJECTIVE
  Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients.
  
  
  METHODS
  Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls.
  
  
  RESULTS
  Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA.
  
  
  CONCLUSIONS
  CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients.
authors.affiliation: Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany. Electronic address: Almanzar_G@ukw.de.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.affiliation: Department of Internal Medicine II, Rheumatology and Immunology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmalzing
authors.affiliation: Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Trippen
authors.affiliation: Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Höfner
authors.affiliation: Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Weißbrich
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Geissinger
authors.affiliation: Pediatric Surgery Unit, Department of Surgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Liese
authors.affiliation: Department of Internal Medicine II, Rheumatology and Immunology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Tony
authors.affiliation: Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Prelog
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000276:immunology; D001171:Arthritis, Juvenile / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D001327:Autoimmune Diseases; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma
keywords: Anti-IL-6; Anti-TNFα; CMV; IFNγ; JIA; RA