T-Cell Homeostatic Imbalance in Placentas From Women With Human Immunodeficiency Virus in the Absence of Vertical Transmission

Abstract

Background Implementation of universal 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 T cell alterations in the placenta contribute to altered immune status in HEU. Methods We analyzed T cells from term placentae decidua and villous tissue and paired cord blood from pregnant women with HIV (PWH) who initiated ART late in pregnancy (n=21) with pregnant women not living with HIV (PWNH) (n=9). Results Placentae from PWH 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. 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.

Impaired CD8+ T cells in term pregnancy decidua with chronic hepatitis B virus infection

“…The immune cell constituents of the maternal‐fetal interface are the maternal immune cells that populate the decidua 30 . A previous study has proved VI contains several fetal immune cells 19 . Therefore, we focused on changes in decidual immune cells to explore the maternal‐fetal interface immune cells variety caused by HBV infection.…”

“…30 A previous study has proved VI contains several fetal immune cells. 19 Therefore, we focused on changes in decidual immune cells to explore the maternal-fetal interface immune cells variety caused by HBV infection. In this study, we found the quantity and quality of CD8 + T cells in the decidua were impaired during the delivery of HBV- The exhaustion of CD8 + T cells has become a representative feature in chronic HBV-infected patients, mainly manifested by the down-regulation of activation signal molecules and the increase of inhibitory molecules, ultimately leading to the reduced antiviral abilities cytotoxicity.…”

“…This divergence might be related to the differences in cell types as the decidua contains the maternal immune cells, while VI contains the immune cells of the fetus. 19 Next, we compared the frequency of placental immune cells between HBV-PW and HC-PW. The results showed that the frequency of total CD3 + T cells and CD8 + T cells in DB and DP of HBV-PW was decreased significantly compared with healthy control, but there was no significant difference in CD4 + T cells; notably, compared with HC-PW, the frequency of B cells in DP was significantly increased in HBV-PW.…”

“…18 Placenta from pregnancies with human immunodeficiency virus (HIV) showed an inverted CD4/CD8 ratio and a higher proportion of tissue-resident CD8 + T cells. 19 Until now, little is known about the CD8 + T cells on the maternal-fetus interface in pregnant women with chronic HBV infection. To this end, it is necessary to delineate the immune profile of CD8 + T cells on the maternal-fetus interface and the role they played in the defense against MTCT of HBV.…”

“…In other virus infections such as human cytomegalovirus, a study has found a significantly delayed lymphoproliferative response observed in mothers who transmitted human cytomegalovirus (HCMV) infection 18 . Placenta from pregnancies with human immunodeficiency virus (HIV) showed an inverted CD4/CD8 ratio and a higher proportion of tissue‐resident CD8 + T cells 19 . Until now, little is known about the CD8 + T cells on the maternal‐fetus interface in pregnant women with chronic HBV infection.…”