TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice.
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.
Wang
H
H
Department of Immunology, Genentech Inc. South San Francisco, CA 94080, USA.
Marsters
S A
SA
Baker
T
T
Chan
B
B
Lee
W P
WP
Fu
L
L
Tumas
D
D
Yan
M
M
Dixit
V M
VM
Ashkenazi
A
A
Grewal
I S
IS
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D003094:Collagen / Q000009:adverse effects; D004195:Disease Models, Animal; D007596:Joints / Q000473:pathology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D053303:Transmembrane Activator and CAML Interactor Protein
D008024:Ligands; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D003094:Collagen