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

Author(s):Show less -

Legrand, Fatema A. ^[1] ; Nixon, Douglas F. ^[2] ; Loo, Christopher P. ^[2] ; Ono, Erika ^[3] ; Chapman, Joan M. ^[2] ; Miyamoto, Maristela ^[3] ; Diaz, Ricardo S. ^[3] ; Santos, Amelia M. N. ^[3] ; Succi, Regina C. M. ^[3] ; Abadi, Jacob ^[4] ; Rosenberg, Michael G. ^[4] ; de Moraes-Pinto, Maria Isabel ^[3] ; Kallas, Esper G. ^[3]

Affiliation

^[1] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 - USA

^[2] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 - USA

^[3] Univ Fed Sao Paulo, Sao Paulo - Brazil

^[4] Albert Einstein Coll Med, Jacobi Med Ctr, Bronx, NY - USA

• Document type: Journal article
• Source: PLoS One; v. 1, n. 1, p. e102, 2006.
• Web of Science Citations: 102

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-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. (AU)