Choi Y, Woo K M, Ko S H, Lee Y J, Park S J, Kim H M, Kwon B S
College of Dentistry, Kangnung National University, Kangnung, Republic of Korea.
Eur J Immunol. 2001 Jul;31(7):2179-88. doi: 10.1002/1521-4141(200107)31:7<2179::aid-immu2179>3.0.co;2-x.
Host immune response is known to contribute to the progression of periodontitis, and alveolar bone destruction in periodontitis is associated with enhanced osteoclast activity. Therefore, we evaluated the roles of activated lymphocyte subsets in osteoclastogenesis. Osteoclast precursors were co-cultured with activated lymphocytes (B, CD4(+) T, CD8(+) T) in the presence of either macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus soluble receptor activator of NF-kappaB ligand (sRANKL), and subsequent differentiation into active osteoclasts was evaluated by a resorption assay. The activated B and CD4(+) cells, but not CD8(+) T cells, induced osteoclast differentiation 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 osteoclasts and increased resorption, while CD8(+) T cells profoundly suppressed osteoclastogenesis. Co-culture using an insert well or supernatant suggested that both B and CD8(+) T cells acted on osteoclasts mostly via soluble proteins. Activated B cells expressed many osteoclastogenic factors including RANKL, TNF-alpha, IL-6, MIP-1alpha, and MCP-3. CD8(+) T cells expressed a substantial amount of osteoprotegerin (OPG) along with RANKL. However, blocking antibody to OPG did not reverse the suppression by CD8(+) T cells, suggesting that other factor(s) are involved. Taken together, activated B cells promoted osteoclastogenesis, while CD8(+) T cells inhibited the osteoclast formation via direct interaction. The results imply the importance of lymphocyte subpopulations in the development of periodontitis.
已知宿主免疫反应会促进牙周炎的进展，且牙周炎中的牙槽骨破坏与破骨细胞活性增强有关。因此，我们评估了活化淋巴细胞亚群在破骨细胞生成中的作用。破骨细胞前体与活化淋巴细胞（B细胞、CD4⁺ T细胞、CD8⁺ T细胞）在单独存在巨噬细胞集落刺激因子（M-CSF）或M-CSF加可溶性核因子κB受体活化因子配体（sRANKL）的情况下共同培养，随后通过吸收试验评估其向活性破骨细胞的分化。单独存在M-CSF时，活化的B细胞和CD4⁺细胞可诱导破骨细胞分化，但CD8⁺ T细胞不能。在存在M-CSF和sRANKL的情况下，B细胞诱导形成小而活性高的破骨细胞并增加吸收，而CD8⁺ T细胞则显著抑制破骨细胞生成。使用插入孔或上清液进行的共培养表明，B细胞和CD8⁺ T细胞大多通过可溶性蛋白作用于破骨细胞。活化的B细胞表达多种破骨细胞生成因子，包括RANKL、肿瘤坏死因子-α、白细胞介素-6、巨噬细胞炎性蛋白-1α和单核细胞趋化蛋白-3。CD8⁺ T细胞除了表达RANKL外，还表达大量骨保护素（OPG）。然而，针对OPG的阻断抗体并不能逆转CD8⁺ T细胞的抑制作用，这表明还涉及其他因素。综上所述，活化的B细胞促进破骨细胞生成，而CD8⁺ T细胞通过直接相互作用抑制破骨细胞形成。这些结果表明淋巴细胞亚群在牙周炎发展中的重要性。
