title: Increased replication of CD4+ naive T cells and changes in T cell homeostasis in a case of acute exacerbation of juvenile idiopathic arthritis: a case comparison study.
abstract: BACKGROUND
  Juvenile idiopathic arthritis is a heterogeneous T cell-mediated autoimmune disease with symptoms of premature aging of the immune system (immunosenescence). The present work is an investigation of immunosenescence parameters, such as quantity of naive and CD28- T cells, T cell receptor excision circles, relative telomere length and alterations of peripheral T cell replication, and was performed via comparison of a case of acute exacerbation of juvenile idiopathic arthritis against six patients with juvenile idiopathic arthritis with disease remission and six age-matched healthy donors over a follow-up course of 12 months.
  
  
  METHODS
  Phenotypical T cell characterization and intracellular interferon γ, tumor necrosis factor α, and interleukin 2 production were studied in peripheral blood mononuclear cells from seven patients with juvenile idiopathic arthritis and six healthy control donors, with findings determined by flow cytometry. T cell receptor excision circles and relative telomere length quantification were performed on deoxyribonucleic acid isolated from naive (CD4+CD28+CD45RA+) T cells and investigated via reverse transcription polymerase chain reaction. Ki67 expression was studied by immunohistochemistry on naive T cells. The non-parametric Mann-Whitney U test and Wilcoxon test for two independent groups of variables were used to compare healthy donors with patients with juvenile idiopathic arthritis. During follow-up, patients with juvenile idiopathic arthritis showed lower total counts of naive and CD28-expressing T cells compared to healthy donors. Acute exacerbation led to low naive and CD28+ T cell populations and elevated proportions of Ki67-expressing CD4+ naive T cells. In conditions of exacerbation, T cell receptor excision circle numbers were in the lower range in patients with juvenile idiopathic arthritis and increased after follow-up. Healthy donors showed significantly higher relative telomere lengths compared to patients with juvenile idiopathic arthritis.
  
  
  CONCLUSIONS
  This investigation illustrates that the changes in T cell homeostasis in patients with juvenile idiopathic arthritis may be the result of several mechanisms, such as diminished thymus function and peripheral exertions to maintain the peripheral T cell pool. The results also demonstrate that hallmarks of immunosenescence such as decreased naive T cell levels and lower T cell receptor excision circle numbers can only be interpreted together with replication markers such as relative telomere length or Ki67 expression.
authors.affiliation: Department of Pediatrics, University of Würzburg, Würzburg, Germany. Almanzar_G@kinderklinik.uni-wuerzburg.de.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.forename: Manuela
authors.initials: M
authors.lastname: Zlamy
authors.forename: Christian
authors.initials: C
authors.lastname: Koppelstaetter
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunner
authors.forename: Verena
authors.initials: V
authors.lastname: Jeller
authors.forename: Christina
authors.initials: C
authors.lastname: Duftner
authors.forename: Christian
authors.initials: C
authors.lastname: Dejaco
authors.forename: Juergen
authors.initials: J
authors.lastname: Brunner
authors.forename: Martina
authors.initials: M
authors.lastname: Prelog