Vδ2 T-cell cytotoxic polarity shift is associated with vascular dysfunction in unexplained recurrent miscarriage: A preliminary study

Abstract

Objective

This study aimed to investigate the link between the cytotoxic profiles of peripheral blood Vδ2 γδT cells and vascular injury in unexplained recurrent miscarriage (URM)

Methods

A total of 30 URM patients and 30 matched healthy controls were enrolled. Using flow cytometry, we analyzed γδT and Vδ2 subsets, and their expression of perforin and granzyme B. Serum levels of vascular injury markers (sFlt-1, sEng, vWF, LDH, VCAM-1) were measured by ELISA.

Results

While no significant differences were observed in the total proportion of γδT cells or in IL-22 expression, URM patients exhibited a marked cytotoxic polarization within the Vδ2 subset: the frequency of Granzyme B⁺Perforin⁺ (GB⁺PF⁺) Vδ2 cells was significantly elevated, whereas GB⁺PF⁻ cells among total γδT and Vδ2 populations were significantly decreased. Concordantly, serum levels of sFlt-1 and vWF were significantly elevated in the URM group, with a trend toward lower sEng. LDH and VCAM-1 did not differ between groups. Importantly, correlation analysis revealed distinct immune–vascular association patterns: sFlt-1 levels were positively correlated with the proportions of GB⁺PF⁻ CD3⁺ and GB⁺PF⁻ γδT cells, whereas vWF levels showed a negative correlation with GB⁺PF⁻ γδT cells but a positive correlation with GB⁺PF⁺ Vδ2 cells.

Conclusion

This study provides preliminary evidence for a cytotoxic polarization of Vδ2 cells in URM, which appears to be associated with markers of vascular injury. These findings identify a potential association between perforin-expressing Vδ2 cells and URM pathogenesis, highlight a novel putative immuno-vascular interaction, and offer hypothesis-generating insights for future investigative and therapeutic strategies.