title: Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal.
abstract: BACKGROUND
  In utero transmission of HIV-1 occurs on average in only 3%-15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4(+) CD25(+) T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children.
  
  
  RESULTS
  We studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4(+) CD25(+) CD127(-) Treg cells and low levels of CD4(+) and CD8(+) T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4(+) CD25(+) Treg cells from the cord blood of EU newborns strikingly augmented both CD4(+) and CD8(+) HIV-1-specific immune responses.
  
  
  CONCLUSIONS
  This study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4(+) CD25(+) T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Fatema A
authors.initials: FA
authors.lastname: Legrand
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Loo
authors.forename: Erika
authors.initials: E
authors.lastname: Ono
authors.forename: Joan M
authors.initials: JM
authors.lastname: Chapman
authors.forename: Maristela
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Diaz
authors.forename: Amélia M N
authors.initials: AM
authors.lastname: Santos
authors.forename: Regina C M
authors.initials: RC
authors.lastname: Succi
authors.forename: Jacob
authors.initials: J
authors.lastname: Abadi
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenberg
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: de Moraes-Pinto
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus