Background: Mother-to-child transmission of HIV-1 occurs in a minority of HIVinfected
mother-infant pairs, even without any interventions. The mechanisms that protect the majority
of HIV-exposed infants from infection are unclear. T regulatory cells (Treg) have important
immunomodulatory functions, but their role in the fetus as well as in mother-to-child transmission of
HIV is under-studied.
Methods: We studied available cryopreserved peripheral blood mononuclear cells from HIVexposed
infants from the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study cohort in Malawi:
64 infants were HIV-uninfected and 28 infants were HIV-infected at birth. We quantified the
frequency of Treg cells (CD4+CD25+FoxP3+), and activated CD4+ and CD8+ T cells (CD38+
HLADR+) by flow cytometry at birth, 6 weeks and 6, 9 and 12 months of age. Descriptive statistics
were performed to describe the distributions of these lymphocyte markers according to the HIV infection
status; and Student’s t tests and Wilcoxon-Rank Sum tests were performed to compare HIVinfected
and uninfected infants.
Results: T cell activation increased rapidly in the first 6 weeks of life, more pronounced on CD8+ T
cells; a further increase in activation was observed at the time of weaning from breastfeeding at 6
months of age. In contrast, the frequency of Treg was stable over the first 6 weeks of life (median,
0.5%), slightly decreased between 6 weeks and 6 months (median at 6 months, 0.3%) and then
slightly increased between 6 months (time of weaning) and 12 months of age (median, 0.45%). HIVinfected
infants had significantly higher frequencies of activated T cells than uninfected infants (P <
0.01). At the time of birth, HIV-exposed uninfected infants had higher levels of Treg, compared to
infants infected in utero, even though this did not reach statistical significance in this small sample
size (P = 0.08).
Conclusion: This study provides initial evidence that Treg may play a role in preventing mother-tochild
transmission of HIV, likely by suppressing immune activation in the fetus and infant, and
needs to be substantiated in a larger study. Better characterization of the role of Treg in fetal and
neonatal immunity may provide a valuable complementary approach to achieve eradication of
mother-to-child transmission of HIV.