title: Memory and naive-like regulatory CD4+ T cells expand during HIV-2 infection in direct association with CD4+ T-cell depletion irrespectively of viremia.
abstract: OBJECTIVE
  The dynamics of CD4(+) regulatory T cells (Treg) during HIV-1 infection remains unclear. To further investigate Treg in this context, we characterized, for the first time, this population in HIV-2-positive individuals. Although both HIV infections are associated with hyperimmune activation and CD4(+) T-cell lymphopenia, most HIV-2-positive individuals display slower disease progression and low-to-undetectable viremia.
  
  
  METHODS
  Samples were obtained from cohorts of untreated HIV-2-positive and HIV-1-positive, treated HIV-1-positive and seronegative individuals. The proportion of CD4(+) T cells bearing a Treg phenotype, defined in terms of high-level CD25 or Foxp3 expression, was assessed by flow cytometry and correlated with markers of disease progression. The proportions of naive and memory-like subsets as well as cycling cells were determined.
  
  
  RESULTS
  We observed an increased proportion of Treg, associated with disease progression, as well as increased proportions of cycling (Ki67(+)) memory Treg, in untreated HIV-2-positive and HIV-1-positive individuals. We also noted an expansion of Treg that persisted over time in treated, immunologically discordant HIV-1-positive individuals, who, similarly to HIV-2-positive patients, present undetectable viremia and low CD4 T-cell count.
  
  
  CONCLUSIONS
  Overall, we demonstrated that Treg frequency was increased in all lymphopenic HIV-2-positive and HIV-1-positive individuals irrespective of the presence or absence of viremia or antiretroviral treatment. This, in turn, suggests that the observed alterations in Treg frequency in HIV/AIDS are more directly related to the degree of CD4 depletion than to viremia.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Foxall
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Albuquerque
authors.forename: Rui S
authors.initials: RS
authors.lastname: Soares
authors.forename: António P
authors.initials: AP
authors.lastname: Baptista
authors.forename: Rita
authors.initials: R
authors.lastname: Cavaleiro
authors.forename: Rita
authors.initials: R
authors.lastname: Tendeiro
authors.forename: Perpétua
authors.initials: P
authors.lastname: Gomes
authors.forename: Rui M M
authors.initials: RM
authors.lastname: Victorino
authors.forename: Ana E
authors.initials: AE
authors.lastname: Sousa
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000821:virology