Immunization with an immunodominant self-peptide derived from glucose-6-phosphate isomerase induces arthritis in DBA/1 mice

Abstract

Introduction T-helper (Th) lymphocytes are critically required for the pathogenesis of glucose-6-phosphate isomerase (G6PI)-induced arthritis, but neither the G6PI epitopes recognized by arthritogenic T cells nor their pathogenic effector functions have been fully elucidated to date. We aimed at identifying arthritogenic G6PI peptides.

Ameliorated course of glucose-6-phosphate isomerase (G6PI)-induced arthritis in IFN-γ receptor knockout mice exposes an arthritis-promoting role of IFN-γ

“…In confirmation of previous reports [18,20], development of G6PI-induced arthritis in wild-type mice was associated with a distinct antibody response to G6PI, encompassing all Ig isotypes (Fig. 2).…”

Regulatory T cells control the transition from acute into chronic inflammation in glucose-6-phosphate isomerase-induced arthritis

“…We used CD154 expression after a brief ex vivo stimulation with G6PI to identify G6PI-specific T cells. CD154 is upregulated within a few hours after T cell receptor triggering and expression of this molecule after brief restimulation is used to identify antigen-specific T cells, independently of their cytokine production 3 10 11 22. A small population (approximately 0.12% of CD4+ cells) expressed CD154 ex vivo after brief restimulation with G6PI 3 days after G6PI immunisation in control mice (figure 2A, upper left panel).…”

“…These effector cells, including B cells, monocyte/macrophages, fibroblasts, neutrophils and mast cells, initiate and maintain a network of cytokines and proinflammatory mediators. We have previously reported that immunisation of non-transgenic mice with the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI) induces severe peripheral symmetrical polyarthritis in normal mice with high incidence (>95%) 1–3. In this model, the development of arthritis depends on T cells, B cells and innate immunity 1–4.…”

Inducible costimulator (ICOS) blockade inhibits accumulation of polyfunctional T helper 1/T helper 17 cells and mitigates autoimmune arthritis

“…Immunisation of DBA/1 mice with the ubiquitous autoantigen glucose-6-phosphate isomerase (G6PI) or a self-peptide derived from the G6PI sequence induces symmetric polyarthritis with a rapid onset and a high incidence,3 4 Importantly, B cells and T cells are critically required for the disease, demonstrated by the inability to induce the disease in B cell-deficient mice and furthermore by the preventive and therapeutic effectiveness of CD4 cell depletion 3 5. Severity of G6PI-induced arthritis can be inhibited by blockade of tumour necrosis factor α (TNFα),3 interleukin 17 (IL17)6 and injection of cytotoxic T lymphocyte antigen 4 (CTLA4) Ig 7…”