Potential Role of Regulatory T Cells in Mother-to-Child Transmission of HIV

Abstract

Background: Mother‐to‐child transmission of HIV‐1 occurs in a minority of HIV‐infected 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 HIV‐exposed 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 HIV‐infected 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%). HIV‐infected 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‐to‐child 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.