Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)This study assessed the immune inflammatory profile and the expression of bone resorption activators receptor activator of nuclear factor kappa B ligand (RANKL) and inhibitor osteoprotegerin (OPG) in apical periodontitis (n = 20) that persisted after root canal retreatment. Methods: Immunohistochemistry was used to characterize lymphocyte populations (CD3(+), CD45R0(+), CD8(+), and FoxP3(+) cells), macrophages (CD68(+)), RANKL(+) and OPG(+) cells in persistent apical periodontitis (PAP) and primary periapical lesions (PPLs). By using quantitative real-time polymerase chain reaction, the mRNA expression of RANKL and OPG in PAP and periodontal ligament from healthy teeth was comparatively analyzed. The data were analyzed by Mann-Whitney, Pearson chi(2), and Wilcoxon tests (5% level). Results: PAP showed an elevated number of FoxP3(+) cells compared with PPL (P < .001). The number of CD68(+) cells was reduced in the PAP samples compared with the PPLs (P < .001). Similar number of other lymphocyte populations was observed in PAP and PPLs (P > .05 for all comparisons). No differences in the RANKL, OPG, and immune-inflammatory cells were demonstrated when comparing PAP microscopically classified as cyst with those classified as granulomas (P > .05 for all comparisons). The assessment of mRNA expression revealed higher levels of RANKL. and OPG in PAP compared with the periodontal ligament from healthy teeth (contiol) samples (P < .001). Also, a greater expression of RANKL in comparison with OPG was observed in PAP (P < .001). Conclusions: These findings indicate that PAP consists of biologically active lesions that demonstrate potential of bone resorption (higher expression of RANKL) and is characterized by an immune-inflammatory cell profile that suggests a suppressive and regulatory environment (higher number of FoxP3(+) cells and lower number of macrophages) favorable to more chronic clinical behavior.423439446National Council for Scientific and Technological Development (CNPq) [474642/2009-7, 306394/2011-1]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)