title: Detectable viral load aggravates immunosenescence features of CD8 T-cell subsets in vertically HIV-infected children.
abstract: BACKGROUND
  CD8 T cells are crucial in the immune responses against HIV infection, but HIV-infected adults suffer a naive CD8 T-cell depletion and accelerated senescence caused by chronic antigen stimulation. Although HIV-infected children preserve a better immune reconstitution capacity their CD8 responses are defective. We wanted to know, whether HIV vertical transmission produces a premature aging of the CD8 population due to antigen exposition to HIV from birth and persistent chronic activation.
  
  
  METHODS
  We conducted a multicentre cross-sectional study that compared vertically HIV-infected children with detectable (viremic) or undetectable (aviremic) viral load and age-matched healthy children. Using multiparameter flow cytometry, we studied within the CD8 population the frequencies of naive, memory, effector memory (effector memory), and TemRA subsets and measured markers of senescence, activation, and proliferation in these cells.
  
  
  RESULTS
  We found that naive subset in viremic children was markedly decreased and had a replicative senescence phenotype. Furthermore, viremic children showed increased frequencies of memory, TEM and TemRA CD8 T cells, with a more activated and replicative senescence phenotype. We found that HIV-infected children with undetectable viral load have an increased senescence in memory and effector CD8 T cells, but the frequencies and phenotype of the CD8 subsets analyzed are comparable to healthy children.
  
  
  CONCLUSIONS
  [corrected] Our study shows that CD8 T cells of HIV-infected children have a more senescent phenotype when compared with age-matched healthy children. Interestingly enough, our results support the importance of maintaining undetectable viral load in HIV-infected children to avoid the premature ageing and dysfunction of CD8 T cells.
authors.affiliation: Laboratorio de InmunoBiología Molecular, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Díaz
authors.forename: Gema
authors.initials: G
authors.lastname: Méndez-Lagares
authors.forename: Rafael
authors.initials: R
authors.lastname: Correa-Rocha
authors.forename: Yolanda María
authors.initials: YM
authors.lastname: Pacheco
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martínez
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.forename: María
authors.initials: M
authors.lastname: del Mar del Pozo-Balado
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: León
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Gurbindo
authors.forename: María
authors.initials: M
authors.lastname: Isabel de José
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
mesh_terms: D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D019562:Viral Load