Radiologic and Immunohistochemical Correlation of Programmed Death 1/Programmed Death Ligand 1 and CD4+ T Cells in Periapical Granuloma and Radicular Cyst: An Observational Study.

AIM: This study quantitatively evaluated CD4+ inflammatory cells, programmed death 1 (PD-1), and its ligand (PD-L1) in periapical granuloma and radicular cyst to elucidate their role in chronic periapical inflammation, and correlated marker expression with periapical index, severity of inflammatory infiltrate and cystic lining thickness.

METHODOLOGY: Eighty-one tissue samples comprising periapical granuloma (PG, n=27), radicular cyst (RC, n=27), healthy pulp (HP, n=14), and normal oral mucosa (NOM, n=13) were evaluated. Morphological and immunohistochemical analyses were performed to quantify CD4, PD-1 and PD-L1 expression with periapical index and histological inflammatory scores. Data were analyzed using non-parametric and Spearman correlation tests (p<.05).

RESULTS

Mean CD4 expression was significantly higher in RC than PG (p < 0.05); both lesions demonstrated higher CD4 levels than HP and NOM (p < 0.05). Conversely, PD-L1 was significantly higher in PG than RC (p< 0.05), HP and NOM (p< 0.001). Notably, PD-1 expression was exclusively observed in PG (p < 0.05). Higher periapical index scores were associated with RC rather than PG (p< 0.001), and its comparison with PD-1 expression was significant (p< 0.001). Severe inflammation equally predominated in PG and RC (p> 0.05). In PGs, inflammatory score correlated significantly with CD4 expression (p= 0.006).

CONCLUSIONS

PG exhibits a highly active immune microenvironment, and the observed expression of PD-1 and PD-L1 may indicate a potential role of the PD-1/PD-L1 checkpoint axis in modulating CD4+T cell-associated inflammation. Conversely, the lack of detectable PD-1 in RC may suggest a divergence in regulatory pathways; however, alternative factors like low localized T-cell activation, sampling variability, or technical limits of detection cannot be excluded.