CEJ, cemento-enamel junction, a landmark for tissue loss; ABC, alveolar bone crest. The distance between CEJ and ABC reflects the amount of tissue or alveolar bone loss measured as described in Methods. (a) A representative tissue section from sham-infected HuPBL-NOD/SCID mice demonstrating the normal periodontal and alveolar bone structures (as in Figure 1b, group II). (b, c) Typical histopathological lesions show significant inflammatory infiltration, connective tissue loss below CEJ (in b), and alveolar bone loss with apical growth of sulcular epithelium below CEJ and into alveolar bone area (in c) in Aa-HuPBL-NOD/SCID mice (as in Figure 2, group II) by the end of 8 weeks. Some multinucleated giant cells (arrows in c) can be observed along the surface of alveolar crestal bone. (d) Mild inflammatory infiltrates without obvious alveolar bone loss, as evidenced by sulcular epithelium located at CEJ, in the periodontal tissues of CD4⁺ T cell–depleted Aa-HuPBL-NOD/SCID mice (as in Figure 2, group III) by the end of 8 weeks. (e, f) In vivo depletion of CD8⁺ T cells (e) (as in Figure 2, group V) or B cells (f) (as in Figure 2, group VI) has no apparent effects on existing periodontal inflammation accompanied by tissue loss below CEJ (in e) or alveolar bone loss with apical growth of sulcular epithelium below CEJ and ABC (in f). These findings are consistent with those observed in nondepleted Aa-HuPBL-NOD/SCID mice in b and c. (g, h) In vivo inhibition of OPG-L via the decoy receptor OPG abrogates alveolar bone destruction, as evidenced by sulcular epithelium located at CEJ and above ABC (in both panels), in Aa-HuPBL-NOD/SCID mice by the end of 8 weeks (as in Figure 4e, group III). Note that OPG treatment does not affect periodontal inflammation observed in g and h. Aa-infected HuPBL-NOD/SCID mice were treated with an OPG-Fc fusion protein as described in Methods. Parts g and h are representative of eight mice studied in this group. Magnifications: a, b, d–h, ×200; c, ×100.