Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal.
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.
Legrand
Fatema A
FA
Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, California, United States of America.
Nixon
Douglas F
DF
Loo
Christopher P
CP
Ono
Erika
E
Chapman
Joan M
JM
Miyamoto
Maristela
M
Diaz
Ricardo S
RS
Santos
Amélia M N
AM
Succi
Regina C M
RC
Abadi
Jacob
J
Rosenberg
Michael G
MG
de Moraes-Pinto
Maria Isabel
MI
Kallas
Esper G
EG
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
D054301:gag Gene Products, Human Immunodeficiency Virus