Placental immune cell distributions of CD4, CD8 and CD56 in the context of SARS-CoV-2 infection and vaccination.

The placenta serves as a crucial immunological interface between mother and fetus, maintaining a delicate balance between immune tolerance and defense. While recent infectious challenges have emphasized changes in systemic immunity, the immune dynamics within the placenta-particularly the interplay between innate and adaptive immune cells-remain less understood. This study investigated how distinct immune exposures during pregnancy influence placental immune cell composition, using SARS-CoV-2 infection and vaccination as model conditions. Placental tissues from 73 women who delivered at the Department of Obstetrics and Gynecology, University Hospital, LMU Munich (April 2020-March 2023) were analyzed immunohistochemically for CD4⁺, CD8⁺, and CD56⁺ markers, representing adaptive and innate immune responses. Participants were categorized into four groups: healthy controls (n = 21), SARS-CoV-2 infection during pregnancy (n = 17), SARS-CoV-2 infection during labor (n = 22), and vaccinated controls (n = 13). Immune markers were quantified separately in fetal villi and maternal decidua, and statistical analyses were performed using Kruskal-Wallis and Mann-Whitney U tests. Placental adaptive immune profiles varied significantly between groups. CD4⁺ cell numbers were higher in the fetal villi of vaccinated individuals compared with those infected during pregnancy (p = 0.001), while CD8⁺ cell levels on the fetal side were reduced (p = 0.046). In contrast, innate immune features-such as macrophage-rich regions and NK-cell density-remained stable across groups, suggesting a preserved innate immune baseline despite systemic activation. These findings reveal distinct adaptive immune modulation following SARS-CoV-2 infection and vaccination and underscore the importance of characterizing both innate and adaptive immune responses to better understand the immunological balance at the maternal-fetal interface.