Depletion of collagen II-reactive T cells and blocking of B cell activation prevents collagen II-induced arthritis in DBA/1j mice

HG Zhang, PA Yang, J Xie, Z Liu, D Liu… - The Journal of …, 2002 - journals.aai.org
HG Zhang, PA Yang, J Xie, Z Liu, D Liu, L Xiu, T Zhou, Y Wang, HC Hsu, JD Mountz
The Journal of Immunology, 2002journals.aai.org
Collagen II (CII)-induced arthritis in DBA/1j mice is mediated by both CII-reactive T cells and
anti-CII Ab-producing B cells. To determine the relative role of these processes in the
development of arthritis, we specifically eliminated CII-reactive T cells by treating the mice
with CII-pulsed syngeneic macrophages that had been transfected with a binary adenovirus
system. These macrophages express murine Fas ligand in a doxycycline-inducible manner
with autocrine suicide inhibited by concomitant expression of p35. The mice were treated iv …
Abstract
Collagen II (CII)-induced arthritis in DBA/1j mice is mediated by both CII-reactive T cells and anti-CII Ab-producing B cells. To determine the relative role of these processes in the development of arthritis, we specifically eliminated CII-reactive T cells by treating the mice with CII-pulsed syngeneic macrophages that had been transfected with a binary adenovirus system. These macrophages express murine Fas ligand in a doxycycline-inducible manner with autocrine suicide inhibited by concomitant expression of p35. The mice were treated iv with four doses of CII-APC-AdFasLp35Tet or a single dose of AdCMVsTACI (5× 10 9 PFU), or both simultaneously, beginning 2 wk after priming with CII in CFA. Treatment with CII-APC-AdFasLp35Tet alone or in combination with a single dose of AdCMVsTACI prevented the development of CII-induced arthritis and T cell infiltration in the joint. The elimination of T cells was specific in that a normal T cell response was observed on stimulation with OVA after treatment with CII-APC-AdFasLp35Tet. Treatment with AdCMVsTACI alone prevented production of detectable levels of circulating anti-CII autoantibodies and reduced the severity of arthritis but did not prevent its development. These results indicate that the CII-reactive T cells play a crucial role in the development of CII-induced arthritis and that the anti-CII Abs act to enhance the development of CII-induced arthritis.
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