Strong HIV-1-Specific T Cell Responses in HIV-1-Exposed Uninfected Infants and Neonates Revealed after Regulatory T Cell Removal

• Autor(a) principal: Legrand, Fatema A.
• Data de Publicação: 2006
• Outros Autores: Nixon, Douglas F., Loo, Christopher P., Ono, Erika [UNIFESP], Chapman, Joan M., Miyamoto, Maristela [UNIFESP], Diaz, Ricardo Sobhie [UNIFESP], Dos Santos, Amelia Miyashiro [UNIFESP], Succi, Regina C. M. [UNIFESP], Abadi, Jacob, Rosenberg, Michael G., Moraes-Pinto, Maria Isabel de [UNIFESP], Kallas, Esper Georges [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1371/journal.pone.0000102; http://repositorio.unifesp.br/handle/11600/29315

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-1specific 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. Methodology/Principal Findings. 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/Significance. 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.