title: Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto's thyroiditis.
abstract: BACKGROUND
  Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto's thyroiditis (HT, n = 18) and healthy controls (HC, n = 70).
  
  
  METHODS
  Proportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization.
  
  
  RESULTS
  Our results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC.
  
  
  CONCLUSIONS
  Patients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for treatment of HT and associated autoimmune diseases.
authors.affiliation: Department of Pediatrics, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, Germany. prelog_m@kinderklinik.uni-wuerzburg.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Prelog
authors.forename: Jörn
authors.initials: J
authors.lastname: Schönlaub
authors.forename: Reinhard
authors.initials: R
authors.lastname: Würzner
authors.forename: Christian
authors.initials: C
authors.lastname: Koppelstaetter
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunner
authors.forename: Martin
authors.initials: M
authors.lastname: Gasser
authors.forename: Rupert
authors.initials: R
authors.lastname: Prommegger
authors.forename: Gabriele
authors.initials: G
authors.lastname: Häusler
authors.forename: Klaus
authors.initials: K
authors.lastname: Kapelari
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Högler