TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice

被引:170
作者
Wang, H
Marsters, SA
Baker, T
Chan, B
Lee, WP
Fu, L
Tumas, D
Yan, MH
Dixit, VM
Ashkenazi, A
Grewal, IS [1 ]
机构
[1] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA
[2] Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA
关键词
D O I
10.1038/89782
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interactions of the tumor necrosis factor superfamily members B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) with their receptors-transmembrane activator and CAML interactor (TACI) and B cell maturation molecule (BCMA)-on B cells play an important role in the humoral immune response. Whereas BCMA is restricted to B cells,TACI is also expressed on activated T cells; we show here that TACI-Fc blocks the activation of T cells in vitro and inhibits antigen-specific T cell activation and priming in vivo. In a mouse model for rheumatoid arthritis (RA), an autoimmune disease that involves both B and T cell components,TACI-Fc treatment substantially inhibited inflammation, bone and cartilage destruction and disease development. Thus, BLyS and/or APRIL are important not only for B cell function but for T cell-mediated immune responses. Inhibition of these ligands might have therapeutic benefits for autoimmune diseases, such as RA, that involve both B and T cells.
引用
收藏
页码:632 / 637
页数:6
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