title: Lymphopenia in patients with chronic idiopathic neutropenia is associated with decreased number of T-lymphocytes containing T-cell receptor excision circles.
abstract: OBJECTIVE
  Chronic idiopathic neutropenia (CIN) is a disorder of granulopoiesis characterized by the presence of activated T-lymphocytes that induce/sustain apoptosis of bone marrow (BM) granulocytic progenitors. T-cell lymphopenia is commonly found in CIN. The aim of the study is to probe the mechanisms underlying T-cell lymphopenia in CIN.
  
  
  METHODS
  We investigated parameters of T-cell homeostasis namely the proliferation/apoptotic rate of naïve and memory T cells, the T-cell senescence by telomere measurement, the recent thymic T-cell production through quantification of T-cell receptor rearrangement excision circles (TRECs), and the production of interleukin (IL)-7.
  
  
  RESULTS
  Patients with CIN (n = 44) displayed lower proportion of naïve CD45RA(+) cells within the CD4(+) and CD8(+) cells compared with controls (n = 15). The proportion of apoptotic cells within the CD8(+) fraction was higher in patients compared with controls and was correlated with the percentage of Ki-67(+) cells, indicating an activation-induced accelerated CD8(+) cell death. The TREC content of CD4(+) and CD8(+) cells was lower in patients compared with controls and was correlated with the proportion of CD45RA(+) CD4(+) and CD8(+) cells and with the levels of serum and BM IL-7, which were significantly decreased in the patients. The mean relative telomere length of CD4(+) and CD8(+) cells was significantly lower in patients with CIN compared with age-matched controls.
  
  
  CONCLUSIONS
  The aberrant T-cell expansions associated with the pathogenesis of CIN result in increased proliferation/apoptosis and possibly exhaustion of peripheral blood T cells which, in association with the inadequate compensatory thymic export of new TREC expressing T cells partially because of IL-7 deficiency, may contribute to lymphopenia in CIN.
authors.affiliation: Department of Haematology, University of Crete School of Medicine, Heraklion, Greece.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gemetzi
authors.forename: Irene
authors.initials: I
authors.lastname: Mavroudi
authors.forename: Helen
authors.initials: H
authors.lastname: Koutala
authors.forename: Maria
authors.initials: M
authors.lastname: Velegraki
authors.forename: Christiana
authors.initials: C
authors.lastname: Choulaki
authors.forename: Athena
authors.initials: A
authors.lastname: Damianaki
authors.forename: Charalampos
authors.initials: C
authors.lastname: Pontikoglou
authors.forename: Helen A
authors.initials: HA
authors.lastname: Papadaki
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D008231:Lymphopenia / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D059506:Telomere Shortening
chemical_list: D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell