Peripheral and Placental KLRG1 + Senescence‐Associated T Cells in Placenta Accreta Spectrum: Diagnostic and Clinical Correlations

ABSTRACT Problem Placenta accreta spectrum (PAS) disorders are considered to be iatrogenic conditions. There is growing evidence for the role of T cell senescence in the pathophysiology of pregnancy complications. This study aimed to investigate peripheral and placental CD4/CD8 T cell subsets and senescence‐associated/highly differentiated T cell frequencies in PAS and to explore their diagnostic performance and correlations with clinical, inflammatory, and proliferative (Ki‐67) parameters. Method of study Placental tissue and maternal peripheral blood were obtained from PAS pregnancies and controls in their third trimester. Flow cytometric immunophenotyping was conducted for peripheral blood and placental CD4/CD8 T cell subsets, senescence‐associated subsets, and their KLRG1 expression intensity. Immunohistochemical analysis of Ki‐67 expression in placental tissue of subjects and controls was performed. Results PAS placental tissue showed an increase in CD28 − CD57 + senescence‐associated, KLRG1 + senescence‐associated T cells, and KLRG1 MFI within all T‐cell compartments. KLRG1 MFI increased progressively toward senescence‐associated (CD28 − CD57 + ) T cell phenotypes across all T‐cell lineages in PAS placental tissue. In contrast, analysis of KLRG1 + percentages in PAS PB revealed limited, largely non‐significant dysregulation of T cells. Ki‐67 expression correlated positively with senescence‐associated DP T cells and KLRG1 + senescence‐associated CD4 + Th cells cells, linking the possible association of trophoblastic proliferation with T‐cell senescence. Conclusion This is the first study analyzing senescence‐associated T cell subsets in PAS patients as well as the previously unexplored double‐positive and double‐negative lineages. Localized immunosenescence at the implantation site may contribute to the pathogenesis of PAS. Senescence‐associated T‐cell signatures show promise as exploratory tissue‐based indicators of the immune dysregulation in PAS.