title: Decreased interleukin 7 responsiveness of T lymphocytes in patients with idiopathic CD4 lymphopenia.
abstract: BACKGROUND
  Elevated serum interleukin 7 (IL-7) levels are observed in lymphopenic conditions, including idiopathic CD4 lymphopenia (ICL), which is characterized by CD4 lymphopenia in the absence of human immunodeficiency virus infection or other known immunodeficiency.
  
  
  METHODS
  To test whether defective IL-7 signaling could be an etiologic or contributing factor in ICL, peripheral blood mononuclear cells from patients with ICL (median CD4 T-cell count, 160 cells/μL) and healthy controls (median CD4 T-cell count, 582 cells/μL) were evaluated for expression of IL-7Rα chain (CD127) and intracellular phosphorylated STAT-5 (a marker of γc cytokine signaling) after cytokine stimulation. Gene expression was analyzed by real-time polymerase chain reaction following IL-7 stimulation.
  
  
  RESULTS
  The percentage of CD4+CD127+ T cells was lower in patients with ICL, compared with controls (P < .001). Lower levels of STAT-5 phosphorylation after IL-7 stimulation were observed in both CD4 and CD8 T cells from patients with ICL, compared with controls (P < .001 and P = .017, respectively), that inversely correlated in CD4 T cells with serum IL-7 levels (r = -0.734, P = .013). Destabilization of p27(kip1), a critical step for IL-7-induced T-cell cycling, was decreased in patients with ICL, compared with controls (P = .004), after IL-7 stimulation.
  
  
  CONCLUSIONS
  These data suggest that diminished responsiveness to IL-7 in CD4 and CD8 T cells during ICL may be contributing to the dysregulation of T-cell homeostasis.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Camille E
authors.initials: CE
authors.lastname: Puronen
authors.forename: William L
authors.initials: WL
authors.lastname: Thompson
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamichi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Beq
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Hodge
authors.forename: Catherine
authors.initials: C
authors.lastname: Rehm
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Parker
authors.forename: Rebecca
authors.initials: R
authors.lastname: DerSimonian
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000097:blood* / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D020395:Receptors, Interleukin-7 / Q000097:blood / Q000235:genetics / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; D051028:bcl-2-Associated X Protein; C415350:interleukin-7 receptor, alpha chain