Unraveling the Immune Puzzle: Study explores Lymphocyte Landscapes in Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) are associated with insufficient remodeling of decidual spiral arteries, leading to maternal and perinatal complications. Recent study analyzed immune differences, specifically lymphocyte subsets, between patients with HDP and normotensive pregnancies, focusing on the implications for vascular remodeling. A total of 173 HDP patients were evaluated alongside healthy control subjects, with an emphasis on immune cell infiltration in the spiral arteries categorized into three groups: acute atherosis (AA), non-remodeled muscular arteries (non-RA), and remodeled arteries (RA).

Immune Cell Quantification and Differences

Immunohistochemical techniques were utilized to quantify infiltrating lymphocytes, revealing significant differences in CD4+ and CD8+ T cell densities. Notably, higher concentrations of both CD4+ and CD8+ T cells were found in the AA group compared to non-RA arteries in HDP patients. Conversely, control subjects showed higher CD4+ T cell densities in non-RA arteries than in remodeled arteries, with no significant differences in the density of CD56+ natural killer (NK) cells between the remodeled and non-remodeled groups. This pattern underscores the association between lymphocyte presence and vascular remodeling status.

Clinical Features of Acute Atherosis in HDP

The incidence of acute atherosis was observed in 32.4% of patients with HDP. Patients exhibiting AA had more severe clinical features, including lower gestational age, birth weight, higher rates of severe proteinuria, and a greater frequency of small-for-gestational-age infants compared to both non-AA HDP patients and healthy controls. Those with AA also demonstrated significant pathological changes, such as distal villous hypoplasia and increased syncytial knots, indicative of placental ischemia.

Role of T Cells and NK Cells in Vascular Remodeling

Findings suggest that elevated CD4+ and CD8+ T cells may contribute to impaired vascular remodeling, potentially modulating cytokine profiles in the spiral artery microenvironment. Moreover, while NK cells predominated in normal pregnancies, their increase in HDP cases with AA could implicate them in the maladaptive immune response affecting spiral artery function.

Implications for Therapeutic Intervention and Understanding of HDP

The study emphasizes the critical role of local immune responses in vascular remodeling processes and the potential for immune disparities to trigger HDP. These insights provide a deeper understanding of the immune mechanisms underlying pregnancy complications and highlight CD4+ T cells and NK cells as potential targets for therapeutic intervention in HDP prevention and management. Overall, the research underscores the interplay between immune profiles and vascular health during pregnancy, elucidating pathways that may contribute to the disease's pathogenesis.

Key Points

- Hypertensive disorders of pregnancy (HDP) result from inadequate remodeling of decidual spiral arteries, leading to significant maternal and neonatal complications; immune differences, specifically in lymphocyte subsets, were analyzed to understand their role in vascular remodeling among 173 HDP patients compared to healthy controls.

- Immunohistochemical analysis demonstrated significant alterations in the densities of CD4+ and CD8+ T lymphocytes; higher levels of both T cell types were present in acute atherosis (AA) cases within the HDP cohort, whereas in controls, CD4+ densities were greater in non-remodeled arteries compared to remodeled arteries, indicating a potential correlation between immune cell infiltration and artery remodeling status.

- Acute atherosis was identified in 32.4% of the HDP patients, characterized by more severe clinical outcomes, including lower gestational age, reduced birth weight, elevated incidences of severe proteinuria, and increased occurrences of small-for-gestational-age infants compared to non-AA HDP patients and controls, highlighting the detrimental effects of AA on pregnancy outcomes.

- Pathological examination of AA cases revealed significant changes such as distal villous hypoplasia and increased syncytial knots, which are associated with placental ischemia, suggesting that local vascular alterations are linked to immune-mediated processes affecting placental health and performance.

- Elevated levels of CD4+ and CD8+ T cells in the spiral artery microenvironment appear to impair vascular remodeling, likely due to modulated cytokine profiles, while an increased presence of natural killer (NK) cells, typically absent in normal pregnancies, implicates them in maladaptive immune responses that may disrupt spiral artery function in cases of acute atherosis.

- The findings highlight the critical role of local immune mechanisms in vascular remodeling related to hypertensive disorders of pregnancy, suggesting potential avenues for immunotherapeutic interventions targeting CD4+ T cells and NK cells to improve maternal and fetal outcomes, while elucidating the pathological pathways indicative of the disease's progression.

Reference –

Ayako Tateishi et al. (2025). Differences In Lymphocyte Subsets Of Spiral Artery Associated With Impaired Vascular Remodeling In Hypertensive Disorders Of Pregnancy. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07653-6.