Requirement of B7 Costimulation for Th1-Mediated Inflammatory Bone Resorption in Experimental Periodontal Disease1
Requirement of B7 Costimulation for Th1-Mediated Inflammatory Bone Resorption in Experimental Periodontal Disease1
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实验性牙周病中 Th1 介导的炎症性骨吸收需要 B7 共刺激 1
作者：
T. Kawai;Ronit Eisen;M. Seki;J. Eastcott;MS Wilson;M. Taubman
TCR信号传导中的CD 28共刺激在调节T细胞反应中发挥着关键作用。为了阐明T细胞在牙周病中的作用，在大鼠中开发了具有TCR/CD 28依赖性Th 1或Th 2克隆的细胞转移系统。牙龈注射特异性Ag、伴放线放线杆菌29-kDa外膜蛋白和LPS可在转移Ag特异性Th 1克隆细胞后10天诱导局部骨吸收，但在转移Th 2克隆细胞后不诱导局部骨吸收。有趣的是，LPS的存在不仅是诱导骨吸收所必需的，而且也是Ag特异性IgG 2a产生所必需的。LPS注射引起牙龈巨噬细胞上B7-1和B7-2表达的诱导表达，否则当动物单独注射Ag时，牙龈巨噬细胞仅表达MHC II类。观察到B7分子的表达长达3天，这对应于T克隆细胞在牙龈组织中保留的持续时间。局部或全身应用CD 28结合B7的功能性拮抗剂CTLA 4 Ig可抑制Th 1克隆细胞联合Ag和LPS刺激诱导的骨吸收。这些结果表明，局部Ag特异性激活的Th 1型T细胞的B7共刺激似乎引发炎性骨吸收，而抑制B7表达的CTLA 4 Ig可能是一种治疗方法干预炎性骨吸收。
The CD28 costimulation at TCR signaling plays a pivotal role in the regulation of the T cell response. To elucidate the role of T cells in periodontal disease, a system of cell transfer with TCR/CD28-dependent Th1 or Th2 clones was developed in rats. Gingival injection of specific Ag, Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein, and LPS could induce local bone resorption 10 days after the transfer of Ag-specific Th1 clone cells, but not after transfer of Th2 clone cells. Interestingly, the presence of LPS was required not only for the induction of bone resorption but also for Ag-specific IgG2a production. LPS injection elicited the induction of expression of both B7-1 and B7-2 expression on gingival macrophages, which otherwise expressed only MHC class II when animals were injected with Ag alone. The expression of B7 molecules was observed for up to 3 days, which corresponded to the duration of retention of T clone cells in gingival tissues. Either local or systemic administration of CTLA4Ig, a functional antagonist of CD28 binding to B7, could abrogate the bone resorption induced by Th1 clone cells combined with gingival challenge with both Ag and LPS. These results suggest that local Ag-specific activation of Th1-type T cells by B7 costimulation appeared to trigger inflammatory bone resorption, whereas inhibition of B7 expression by CTLA4Ig might be a therapeutic approach for intervention with inflammatory bone resorption.
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DOI：
--
发表时间：
1998-04
期刊：
The American journal of pathology
影响因子：
--
作者：
E. Gravallese;Y. Harada;Jeng-Tzang Wang;A. Gorn;T. Thornhill;S. Goldring
通讯作者：
E. Gravallese;Y. Harada;Jeng-Tzang Wang;A. Gorn;T. Thornhill;S. Goldring
影响因子：
4.4
作者：
T. Kawai;M. Seki;K. Hiromatsu;J. Eastcott;G. Watts;M. Sugai;D. Smith;S. Porcelli;M. Taubman
通讯作者：
T. Kawai;M. Seki;K. Hiromatsu;J. Eastcott;G. Watts;M. Sugai;D. Smith;S. Porcelli;M. Taubman
影响因子：
15.9
作者：
AbuAmer, Y;Ross, FP;Teitelbaum, SL
通讯作者：
Teitelbaum, SL
DOI：
--
发表时间：
1998
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
JanewayJr,CA
通讯作者：
JanewayJr,CA
通过长期阻断 CD28-B7 相互作用并去除移植周围 T 细胞，使大鼠至小鼠心脏异种移植物长期存活。
影响因子：
3.8
作者：
Rehman,A;Tu,Y;Arima,T;Linsley,PS;Flye,MW
通讯作者：
Flye,MW