CD4+T-Cells cause cognitive dysfunction in preeclampsia or COVID-19 infection in a pregnant rat model

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with increased cerebral blood flow (CBF), impaired cognitive function, and memory loss. We have shown adoptive transfer of placental CD4+ T cells from PE women into athymic nude pregnant rats causes HTN and increased circulating factors associated with PE. COVID-19 (CV) during pregnancy is associated with increased diagnosis of PE. However, the role of CD4+ T cells stimulated in response to CV in contributing to the PE phenotype in patients with a Hx of CV during pregnancy is unknown. We hypothesize adoptive transfer of placental CD4+ T cells from patients with a CV History (Hx) during pregnancy with PE causes HTN, CBF alterations, and cognitive dysfunction in pregnant athymic nude recipient rats. Placental CD4+ T cells were isolated from normotensive (NP), PE, Hx of CV normotensive (CV Hx NT), and Hx of CV with PE (CV Hx+PE) at delivery. One million CD4+ T cells were injected i.p. into nude athymic rats on gestational day (GD) 12. A Barnes maze and the novel object recognition assays were used to assess cognitive function on GDs 15-19. Blood pressure (MAP) and CBF were measured by carotid catheter and laser Doppler flowmetry on GD19, respectively. A two-way ANOVA was used for statistical analysis. MAP increased in CV Hx+PE (111±4, n=4) and PE recipient rats (115±2 mmHg, n=5) compared to CV Hx NT (100±4, n=5) and NP (99±3 mmHg, n=4 p< 0.05). CV Hx+PE and PE exhibited greater latency with more errors in the Barnes maze compared to CV Hx NT and NP groups. Locomotor activity was decreased in CV Hx+PE (P< 0.05) compared to PE, CV Hx NT, and NP groups. CV Hx+PE and PE exhibited short term memory dysfunction compared to CV Hx NT and NP groups. PE and CV Hx+ PE had impaired autoregulation of CBF compared to CV Hx NT and NP rats. Our findings indicate that pregnant recipients of CD4+ T cells from PE with or without a Hx CV during pregnancy cause HTN, impaired CBF and cognitive dysfunction compared to recipients of NP or NT Hx COVID-19 CD4 + T cells.