Nadia M Ikumi1, Komala Pillay2,3, Tamara Tilburgs4,5, Thokozile R Malaba6, Sonwabile Dzanibe1, Elizabeth Ann L Enninga7, Rana Chakraborty7,8,9, Mohammed Lamorde10, Landon Myer6, Saye Khoo11, Heather B Jaspan1, Clive M Gray1,2,12. 1. Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 2. National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa. 3. Division of Anatomical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa. 4. Division of Immunobiology, Center for Inflammation and Tolerance, Cincinnati Children's Hospital, Cincinnati, Ohio, USA. 5. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. 6. Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. 7. Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA. 8. Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Minnesota, USA. 9. Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA. 10. Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda. 11. Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom; Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom. 12. Department of Pathology, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: Implementation of universal antiretroviral therapy (ART) has significantly lowered vertical transmission rates but has also increased numbers of human immunodeficiency virus (HIV)-exposed uninfected children, who remain vulnerable to morbid effects. In the current study, we investigated whether T-cell alterations in the placenta contribute to altered immune status in HIV-exposed uninfected. METHODS: We analyzed T cells from term placenta decidua and villous tissue and paired cord blood from pregnant women living with HIV (PWH) who initiated ART late in pregnancy (n = 21) with pregnant women not living with HIV (PWNH) (n = 9). RESULTS: Placentas from PWH showed inverted CD4/CD8 ratios and higher proportions of tissue resident CD8+ T cells in villous tissue relative to control placentas. CD8+ T cells in the fetal capillaries, which were of fetal origin, were positively correlated with maternal plasma viremia before ART initiation, implying that imbalanced T cells persisted throughout pregnancy. In addition, 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. CONCLUSIONS: T-cell homeostatic imbalance in the blood circulation of PWH 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.
BACKGROUND: Implementation of universal antiretroviral therapy (ART) has significantly lowered vertical transmission rates but has also increased numbers of human immunodeficiency virus (HIV)-exposed uninfected children, who remain vulnerable to morbid effects. In the current study, we investigated whether T-cell alterations in the placenta contribute to altered immune status in HIV-exposed uninfected. METHODS: We analyzed T cells from term placenta decidua and villous tissue and paired cord blood from pregnant women living with HIV (PWH) who initiated ART late in pregnancy (n = 21) with pregnant women not living with HIV (PWNH) (n = 9). RESULTS: Placentas from PWH showed inverted CD4/CD8 ratios and higher proportions of tissue resident CD8+ T cells in villous tissue relative to control placentas. CD8+ T cells in the fetal capillaries, which were of fetal origin, were positively correlated with maternal plasma viremia before ART initiation, implying that imbalanced T cells persisted throughout pregnancy. In addition, 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. CONCLUSIONS: T-cell homeostatic imbalance in the blood circulation of PWH 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.
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