title: Loss of IL-7Ralpha is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients.
abstract: OBJECTIVE
  Elevated levels of interleukin (IL)-7 are present in the blood of HIV-positive patients and it is known that IL-7 receptor (IL-7R)alpha expression decreases on T cells during HIV infection. The subset(s) of T cells with low IL-7Ralpha and the consequence of low IL-7Ralpha expression for T-cell survival are poorly characterized.
  
  
  METHODS
  The frequency of IL-7Ralpha-negative T cells in HIV-positive patients was studied in relation to CD4 T-cell counts, IL-7 concentration and survival in culture. We analysed IL-7Ralpha expression in different T-cell populations and in relation to Bcl-2 expression.
  
  
  METHODS
  Specimens from 38 HIV-1 patients and 17 controls were examined. IL-7Ralpha and Bcl-2 expression in different T-cell populations was studied by flow cytometry. The influence of IL-7Ralpha expression on T-cell survival was studied by culturing T cells in the presence of IL-7.
  
  
  RESULTS
  Down-regulation of IL-7Ralpha on T cells correlated with depletion of CD4 T cells (P < 0.001) and also with increased concentration of serum IL-7 (P < 0.05). The decreased IL-7Ralpha expression was associated with low Bcl-2 expression and with the reduced survival capacity of T cells in the presence of IL-7 in vitro. Particularly, T cells with memory phenotype showed a decreased IL-7Ralpha expression in association with CD28 down-regulation.
  
  
  CONCLUSIONS
  The positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIV-infected individuals due to IL-7Ralpha down-regulation. Differentiation towards a CD28-negative memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. Bence.Rethi@mtc.ki.se
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
authors.forename: Caroline
authors.initials: C
authors.lastname: Fluur
authors.forename: Ann
authors.initials: A
authors.lastname: Atlas
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krzyzowska
authors.forename: Frida
authors.initials: F
authors.lastname: Mowafi
authors.forename: Sven
authors.initials: S
authors.lastname: Grützmeier
authors.forename: Angelo
authors.initials: A
authors.lastname: De Milito
authors.forename: Rino
authors.initials: R
authors.lastname: Bellocco
authors.forename: Kerstin I
authors.initials: KI
authors.lastname: Falk
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavölgyi
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D018106:CD28 Antigens / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood / Q000494:pharmacology; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D015851:Interleukin-7; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain