HIV This Week

Legrand FA, Nixon DF, Loo CP, Ono E, Chapman JM, Miyamoto M, Diaz RS, Santos AM, Succi RC, Abadi J, Rosenberg MG, de Moraes-Pinto MI, Kallas EG. Strong HIV-1-Specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal. PLoS ONE 2006;1:e102.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17183635

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. It was 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. Legrand and colleagues assessed whether T-regulatory cells could suppress HIV-1-specific immune responses in young children. The authors studied two cohorts of children. The first group included HIV-1-exposed-uninfected as well as unexposed neonates. The second group comprised HIV-1-infected and HIV-1-exposed-uninfected children. They quantified the frequency of T-regulatory cells, T-cell activation, and cell-mediated immune responses. The authors detected high levels of CD4(+)CD25(+)CD127(-) T-regulatory cells and low levels of CD4(+) and CD8(+) T cell activation in the cord blood of the HIV-1-exposed-uninfected neonates. They 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(+) T-regulatory cells from the cord blood of HIV-1-exposed-uninfected newborns strikingly augmented both CD4(+) and CD8(+) HIV-1-specific immune responses. The authors conclude that they provide new evidence that HIV-1-exposed-uninfected 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.

Editors’ note: Understanding how and why some exposed infants do not get infected during pregnancy and labour is critical to the development of neonatal vaccines.