Osteoclastogenesis is enhanced by activated B cells but suppressed by activated CD8(+) T cells

Host immune response is known to contribute to the progression of periodont itis, and alveolar bone destruction in periodontitis is associated with enh anced osteoclast activity. Therefore, we evaluated the roles of activated l ymphocyte subsets in osteoclastogenesis. Osteoclast precursors were co-cult ured with activated lymphocytes (B, CD4(+) T, CD8(+) T) in the presence of either macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus sol uble receptor activator of NF-kappaB ligand (sRANKL), and subsequent differ entiation into active osteoclasts was evaluated by a resorption assay. The activated B and CD4(+) cells, but not CD8(+) T cells, induced osteoclast di fferentiation in the presence of M-CSF alone. In the presence of M-CSF and sRANKL, B cells induced the formation of small but highly active osteoclast s and increased resorption, while CD8(+) T cells profoundly suppressed oste oclastogenesis. Go-culture using an insert well or supernatant suggested th at both B and CD8+ T cells acted on osteoclasts mostly via soluble proteins . Activated B cells expressed many osteo-clastogenic factors including RANK L, TNF-alpha, IL-6, MIP-1 alpha, and MCP-3. CD8(+) T cells expressed a subs tantial amount of osteoprotegerin (OPG) along with RANKL. However, blocking antibody to OPG did not reverse the suppression by CD8(+) T cells, suggest ing that other factor(s) are involved. Taken together, activated B cells pr omoted osteoclastogenesis, while CD8(+) T cells inhibited the osteoclast fo rmation via direct interaction. The results imply the importance of lymphoc yte subpopulations in the development of periodontitis.