T cell Homeostatic Imbalance in Placentae from Women Infected with HIV in the absence of Vertical Transmission.

Background: Implementation of Option B+ antiretroviral therapy (ART) has significantly lowered vertical transmission rates but has also increased numbers of HIV-exposed uninfected children (HEU), who remain vulnerable to morbidities. Here, we investigated whether altered immune status in HEU originates in the placenta. Methods: We analyzed T cells from term placentae decidua and villous tissue and paired cord blood from pregnant women living with HIV (PWLWH) who initiated ART late in pregnancy (n=21) with HIV negative controls (n=9). Results: Placentae from PWLWH showed inverted CD4:CD8 ratios and higher proportions of tissue resident CD8+ T cells in villous tissue relative to control placentae. CD8+ T cells in the fetal capillaries, which were of fetal origin, positively correlated with maternal plasma viraemia prior to ART initiation, implying that imbalanced T cells persisted throughout pregnancy. Additionally, the expanded memory differentiation of CD8+ T cells was confined to the fetal placental compartment and cord blood, but was not observed in the maternal decidua. Conclusion: T cell homeostatic imbalance in the blood circulation of PWLWH is reflected in the placenta. The placenta may be a causal link between HIV-induced maternal immune changes during gestation and altered immunity in newborn infants in the absence of vertical transmission.