T Cell Influence on Superantigen‐Induced Arthritis in MRL‐lpr/lpr Mice

Publisher Website
Google Scholar
Abstract
Objective. To define the influence of the T cell receptor (TCR) and the lpr autoimmune gene on the induction and progression of superantigen‐induced arthritis in V β8 transgenic MRL‐lpr/lpr mice. Methods. The time to onset and the extent of synovial hyperplasia after the induction of arthritis by intraarticular injection of staphylococcal enterotoxin B (SEB) were compared in mice having T cells that bear the V β8 transgene alone (V β8 TCR transgenic MRL‐+/+), the lpr gene without the V β8 gene (nontransgenic MRL‐lpr/lpr), both the V β8 gene and the lpr gene (V β8 transgenic MRL‐lpr/lpr), or neither gene (nontransgenic MRL‐+/+). Synovial hyperplasia was compared in SEB‐injected V β8 transgenic MRL‐lpr/lpr mice after treatment with cyclosporin A (CSA), anti‐V β8 and anti‐CD4 monoclonal antibodies, and in V β8 transgenic MRL‐lpr/lpr mice after injection of a non—V β8‐reactive superantigen, staphylococcal enterotoxin A (SEA). Results. At day 30, increased synovial cells were observed in all SEB‐treated mice, but the increase was greatest in the V β8 transgenic MRL‐lpr/lpr mice. T cell involvement was indicated by the inability of either heat‐denatured SEB or SEA to induce severe arthritis, the reduction in the severity of the arthritis on systemic treatment with CSA or anti‐V β8, and the correlation of synovial hyperplasia with in vitro SEB reactivity of T cells. Conclusion. These observations suggest that super‐antigens can induce chronic arthritis and that the induction and progression of the arthritis requires an underlying T cell defect in anergy induction in addition to exposure to the superantigen.

This publication has 72 references indexed in Scilit: