Tracking of Proinflammatory Collagen-Specific T Cells in Early and Late Collagen-Induced Arthritis in Humanized Mice

Svendsen, Pia; Andersen, Claus B.; Willcox, Nick; Coyle, Anthony J.; Holmdahl, Rikard; Kamradt, Thomas; Fugger, Lars

doi:10.4049/jimmunol.173.11.7037

Cited by 36 publications

(36 citation statements)

References 55 publications

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“…Thus, the mice are affected by arthritis through a Th2-like pathway. It has been shown before that in conventional CIA the CII-specific CD4 ϩ T cells found in the joint are mainly Tim-3 ϩ /IL-33R Ϫ , suggesting a Th1 phenotype (35). In this model, it is largely IL-33R ϩ CD4 ϩ T cells that seem to mediate pathogenicity, which is clearly different from conventional, adjuvant-dependent CIA.…”

Section: Discussionmentioning

confidence: 80%

Ncf1-Associated Reduced Oxidative Burst Promotes IL-33R+ T Cell-Mediated Adjuvant-Free Arthritis in Mice

Hagenow

Gelderman

Hultqvist

et al. 2009

The Journal of Immunology

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Reactive oxygen species (ROS) are important in the immune defense against invading pathogens, but they are also key molecules in the regulation of inflammatory reactions. Low levels of ROS production due to a polymorphism in the neutrophil cytosolic factor 1 (Ncf1) gene are associated with autoimmunity and arthritis severity in mouse models induced with adjuvant. We established an adjuvant-free arthritis model in which disease is induced by injection of the autoantigen collagen type II (CII) and depends on IL-5-producing T cells and eosinophils. In addition, the transgenic expression of mutated mouse CII allowed us to investigate an autoreactive immune response to an autologous Ag and by that natural tolerance mechanism. We show that a deficient ROS production, due to a spontaneous mutation in Ncf1, leads to increased autoantibody production and expansion of IL-33R-expressing T cells, impaired T cell tolerance toward tissue-specific CII, and severe arthritis in this unique model without disturbing adjuvant effects. These results demonstrate that the insufficient production of ROS promotes the breakdown of immune tolerance and development of autoimmune and adjuvant-free arthritis through an IL-5- and IL33R-dependent T cell activation pathway.

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Section: Discussionmentioning

confidence: 80%

Ncf1-Associated Reduced Oxidative Burst Promotes IL-33R+ T Cell-Mediated Adjuvant-Free Arthritis in Mice

Hagenow

Gelderman

Hultqvist

et al. 2009

The Journal of Immunology

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“…Soluble HLA-DR2b was expressed in Drosophila S2 cells, and HLA-DM were prepared as described previously (Svendsen et al, 2004;Sloan et al, 1995). TCR V a and V b regions were PCR amplified from cDNA derived from the Ob.1A12 T cell hybridoma and spliced by overlap extension to TCR C a and C b regions, including C-terminal extensions designed to assist the formation of an interchain disulfide bridge (Stewart-Jones et al, 2003).…”

Section: Protein Preparation For Crystallization Purposesmentioning

confidence: 99%

T Cell-Mediated Autoimmune Disease Due to Low-Affinity Crossreactivity to Common Microbial Peptides

et al. 2009

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Environmental factors account for 75% of the risk of developing multiple sclerosis (MS). Numerous infections have been suspected as environmental disease triggers, but none of them has consistently been incriminated, and it is unclear how so many different infections may play a role. We show that a microbial peptide, common to several major classes of bacteria, can induce MS-like disease in humanized mice by crossreacting with a T cell receptor (TCR) that also recognizes a peptide from myelin basic protein, a candidate MS autoantigen. Structural analysis demonstrates this crossreactivity is due to structural mimicry of a binding hotspot shared by self and microbial antigens, rather than to degenerate TCR recognition. Biophysical studies reveal that the autoreactive TCR binding affinity is markedly lower for the microbial (mimicry) peptide than for the autoantigenic peptide. Thus, these data suggest a possible explanation for the difficulty in incriminating individual infections in the development of MS.

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“…19 IL-6 and TNF-a are increased in arthritic joints, and IL-17 is required for arthritis in this model. 18,25,36 T cells are important in the pathogenesis of human RA 8,30,49,55 and are central to the pathogenesis of arthritis in IL-1RA knockout mice: Whereas T cell-deficient IL-1RA knockout mice do not develop arthritis, T-cell transfer from IL-1RA knockout mice to (T-cell deficient) nude mice induces arthritis.…”

Section: Spontaneous (Including Genetically Engineered) Modelsmentioning

confidence: 99%

Mouse Models of Rheumatoid Arthritis

Caplazi¹,

Baca²,

Barck³

et al. 2015

Vet Pathol

117

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Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody-induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFD ARE mouse, in which arthritis results from overexpression of TNF-a, a master proinflammatory cytokine that drives disease in many patients.

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Tracking of Proinflammatory Collagen-Specific T Cells in Early and Late Collagen-Induced Arthritis in Humanized Mice

Cited by 36 publications

References 55 publications

Ncf1-Associated Reduced Oxidative Burst Promotes IL-33R+ T Cell-Mediated Adjuvant-Free Arthritis in Mice

Ncf1-Associated Reduced Oxidative Burst Promotes IL-33R+ T Cell-Mediated Adjuvant-Free Arthritis in Mice

T Cell-Mediated Autoimmune Disease Due to Low-Affinity Crossreactivity to Common Microbial Peptides

Mouse Models of Rheumatoid Arthritis

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