| We are using the feline immunodeficiency virus (FIV)-infected cat to model HIV mother-to-child-transmission (MTCT). Vertical transmission of either virus may result not only in infected offspring, but also failed pregnancy. In HIV infections, maternal hematological and virological parameters predict MTCT. We hypothesized that such parameters would likewise be predictors of FIV vertical transfer. We inoculated ten cats with FIV-B-2542; 10 cats were uninoculated. Cats were allowed to breed naturally. Fetuses were delivered at approximately week 3 (early) gestation by cesarean section. Fetal and placental tissues were collected. Blood samples were collected from the day of inoculation through delivery. We quantified CD4:CD8 T cell ratios, proviral load, and plasma viremia, and monitored seroreactivity to FIV proteins in longitudinal sera from both groups of cats. We documented clinical and reproductive outcome. The infected group produced reduced litter size and more failed pregnancies; CD4:CD8 ratios were depressed by 3.5 months p.i. Proviral DNA was detected in 14 of 14 (100%) placentas tested and 12 of 14 (86%) fetuses. However, the parameters assessed were not predictive of reproductive outcome and suggested a role for placental immunopathology in compromised pregnancy. Regulatory T cells (Treg) are anti-inflammatory and essential in maintaining pregnancy.Th17 cells are pro-inflammatory and associated with pregnancy failure. The activation of these cell populations is regulated by the cytokines TGF-β and IL-6. We hypothesized that placental immunology may result from altered dynamics of these cell populations. Using immunofluorescence confocal microscopy to measure Treg and Th17 markers FoxP3 and RORγ, respectively, we quantified these cells in placental specimens from FIV-infected and control cats at early and late (week 8) gestation. Significantly higher levels of RORγ were measured in FIV-infected placentas at early pregnancy; these cells co-localized at the maternal-fetal interface. We quantified the expression of Treg immunomodulators by quantitative PCR, noting higher expression of TGF-β in infected queens. A positive correlation of RORγ with IL-6 occurred in control placentas, as predicted, but not in infected placentas. Collectively, the data suggest that an inflammatory placental microenvironment at early pregnancy in infected queens may result, in part, from dysregulation of the Treg/Th17 balance. |
