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

Abstract

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.

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Figure 1: TACI-Fc inhibits T cell stimulation in vitro.
Figure 2: TACI-Fc inhibits antigen-specific T cell responses in vivo.
Figure 3: TACI-Fc treatment inhibits collagen-induced arthritis in mice.
Figure 4: TACI-Fc inhibits joint damage in CIA. DBA/1 mice were immunized and treated with TACI-Fc or control IgG.
Figure 5: TACI-Fc ameliorates the severity of arthritis development.
Figure 6: TACI-Fc inhibits anti-collagen immune responses.

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Acknowledgements

We thank L. Closkey, T. Echevery, R. Pitti, M. Nagel and P. Haas for help with TACI-Fc protein expression and purification and I. Roth for assistance.

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Correspondence to Avi Ashkenazi or Iqbal S. Grewal.

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Wang, H., Marsters, S., Baker, T. et al. TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice. Nat Immunol 2, 632–637 (2001). https://doi.org/10.1038/89782

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