Analysis of CD4+ and CD8+ T Lymphocytes and Expression of Immune Checkpoint Proteins (PD-1 and PD-L1) in Primary and Persistent Periapical Lesions.

INTRODUCTION

Persistent periapical lesions (PePL) represent a clinical challenge because of their inadequate response to conventional endodontic therapies. Studies indicate differences in immunoinflammatory mechanisms between primary periapical lesions (PrPL) and PePL but the findings remain conflicting. This study aimed to evaluate CD4+ and CD8+ T lymphocytes and the expression of immune checkpoint proteins (programmed cell death protein 1 [PD-1] and its ligand [PD-L1]) in PrPL and PePL, correlating the findings with the intensity of the inflammatory infiltrate and pattern of the cystic epithelial lining.

METHODS

Ten primary radicular cysts, 10 persistent radicular cysts (PeRC), 10 primary periapical granulomas (PrPG), and 10 persistent periapical granulomas were submitted to immunohistochemical analysis using anti-CD8, anti-CD4, anti-PD-1, and anti-PD-L1 antibodies.

RESULTS

Higher median T lymphocyte counts were observed in PeRC when compared to the other groups, with a statistically significant difference in CD8+ T cells compared to PrPG (P < .05). Regarding PD-L1, PeRC exhibited higher median percentages of positivity in connective tissue and epithelial lining, which differed significantly from the other groups (P < .005). There were no statistically significant differences in the numbers of CD4+ or CD8+ T lymphocytes nor in the expression of PD-1 or PD-L1 according to morphologic parameters (P > .05). Immunoexpression of PD-L1 and CD4+ T lymphocyte count showed a positive correlation in PrPL (r = .592; P < .005) and PePL (r = .532; P < .05). In the latter, PD-L1 and CD8+ T lymphocyte count were also positively correlated (r = .690; P < .001).

CONCLUSIONS

The results suggest the involvement of PD-1 and PD-L1 in the regulation of immunoinflammatory responses in PrPL and PePL. These immune checkpoint proteins may be particularly important for the suppression of CD4+ and CD8+ T lymphocyte activities in the periapical lesions studied, contributing to their chronicity.