title: Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery.
abstract: BACKGROUND
  High levels of ex vivo CD4 T-cell death and the accumulation of highly differentiated and/or immunosenescent T cells have been associated with poor CD4 T-cell recovery in treated HIV-infected individuals. However, the relationship between cell death and T-cell differentiation is still unclear.
  
  
  METHODS
  We have analyzed cell death, immunosenescence and differentiation parameters in HAART-treated subjects (VL <50 copies/mL for more than 2 years) with CD4 T-cell count <350 cells/μL (immunodiscordant, n = 23) or >400 cells/μL (immunoconcordant, n = 33). We included 11 healthy individuals as reference.
  
  
  RESULTS
  As expected, suboptimal CD4 T-cell recovery was associated with low frequencies of naïve cells, high frequencies of transitional and effector memory cells and a subsequent low ratio of central/transitional memory cells in the CD4 compartment. These alterations correlated with spontaneous CD4 T-cell death. A deeper analysis of cell death in CD4 T-cell subsets showed increased cell death in memory cells of immunodiscordant individuals, mainly affecting central memory cells. Immunosenescence was also higher in immunodiscordant individuals albeit unrelated to cell death. The CD8 compartment was similar in both HIV-infected groups, except for an underrepresentation of naïve cells in immunodiscordant individuals.
  
  
  CONCLUSIONS
  Immunodiscordant individuals show alterations in memory CD4 T-cell differentiation associated with a short ex vivo lifespan of central memory cells and an in vivo low central/transitional memory cell ratio. These alterations may contribute to poor CD4 T-cell repopulation.
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. marta.massanella@gmail.com.|Department of Pathology, University of California San Diego, La Jolla, CA, 92093, USA. marta.massanella@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. egomez@irsicaixa.es.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Gómez-Mora
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. jcarrillo@irsicaixa.es.
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrillo
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. mcurriu@irsicaixa.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Curriu
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. douchi@irsicaixa.es.
authors.forename: Dan
authors.initials: D
authors.lastname: Ouchi
authors.affiliation: Fundació Lluita contra la SIDA, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, 08916, Badalona, Spain. jpuig@flsida.org.
authors.forename: Jordi
authors.initials: J
authors.lastname: Puig
authors.affiliation: Fundació Lluita contra la SIDA, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, 08916, Badalona, Spain. enegredo@flsida.org.|Universitat de Vic-Central de Catalunya, UVIC-UCC, 08500, Vic, Spain. enegredo@flsida.org.
authors.forename: Eugènia
authors.initials: E
authors.lastname: Negredo
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. ccabrera@irsicaixa.es.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cabrera
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. bclotet@irsicaixa.es.|Fundació Lluita contra la SIDA, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, 08916, Badalona, Spain. bclotet@irsicaixa.es.|Universitat de Vic-Central de Catalunya, UVIC-UCC, 08500, Vic, Spain. bclotet@irsicaixa.es.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain. jblanco@irsicaixa.es.|Universitat de Vic-Central de Catalunya, UVIC-UCC, 08500, Vic, Spain. jblanco@irsicaixa.es.
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D018959:CD57 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002451:Cell Compartmentation; D016923:Cell Death; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D018959:CD57 Antigens