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Ann Rheum Dis. Oct 2003; 62(10): 983–990.
PMCID: PMC1754310

IFNγ deficient C57BL/6 (H-2b) mice develop collagen induced arthritis with predominant usage of T cell receptor Vß6 and Vß8 in arthritic joints


Background: Transgenic deficiency in interferon γ (IFNγ) or IFNγ receptor makes resistant strains of mice bearing H-2b or H-2d susceptible to collagen induced arthritis (CIA).

Objective: To determine whether the escape from regulation of disease susceptibility at the major histocompatibility complex level involves a new use of autoimmune T cells expressing T cell receptor (TCR) Vß that vary from the cell populations previously identified within arthritic joints.

Methods: Arthritis was induced by a standard protocol with type II bovine collagen (CII) in complete Freund's adjuvant. Clinical features, histopathology, immunological responses, and TCR profile in arthritic joints in IFNγ knockout C57BL/6 (B6.IFNγ KO) mice (H-2b) were compared directly with those in DBA/1 mice (H-2q).

Results: 60–80% of B6.IFNγ KO mice developed a progressive arthritis with a similar clinical course to classical CIA in DBA/1 mice. The affected joints in B6.IFNγ KO mice had an erosive form of arthritis with similar features to joint disease in DBA/1 mice. B6.IFNγ KO mice produced significantly higher levels of IgG2b and IgG1 autoantibodies to murine CII and showed increased proliferative response to CII compared with B6 mice. Comparable levels of interleukin 1ß and tumour necrosis factor α expression were detected in arthritic joints from ß6.IFNγ KO and DBA/1 mice. B6.IFNγKO mice used predominantly TCR Vß6 and Vß8 in arthritic joints. This TCR Vß profile is similar to that found in DBA/1 mice with CIA.

Conclusions: C57BL/6 mice deficient in IFNγ production can develop arthritis that resembles classical CIA. These data suggest that IFNγ is a key factor mediating susceptibility to CIA.

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Selected References

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Figures and Tables

Figure 1
Arthritis in B6.IFNγ KO mice immunised with bovine CII in CFA. (A) An arthritic hind paw of a B6.IFNγ KO mouse at day 3 of arthritis with a clinical score 1. There is substantial erythematous oedema from the ankle through the digits. ...
Figure 2
Natural clinical course of arthritis in B6.IFNγ KO mice. The average clinical score of arthritic mice reflects the clinical severity of an individual arthritic limb and the number of affected limbs. DBA/1 mice exhibited a typical monophasic progressive ...
Figure 3
Histopathology of arthritis in B6.IFNγ KO mice. (A) Section of a hind paw with arthritis at the day of onset showing inflamed synovium with massive infiltrate of mononuclear cells. There is decreased number of chondrocytes in the articular cartilage. ...
Figure 4
Levels of anti-heterologous and autologous CII antibodies in B6.IFNγ KO mice immunised with bovine CII in CFA (n=10 mice in each group). *p<0.01 (B6.IFNγ KO v B6); **p<0.05 (B6.IFNγ KO v B6).
Figure 5
Enhanced proliferation of lymphocytes from CII immunised B6.IFNγ KO mice. Results are representative of three experiments; n=3 in each group.
Figure 6
Expression of cytokines in arthritic joints in B6.IFNγ KO mice. IL1ß and TNFα gene expression was quantified using a quantitative real-time RT-PCR. Levels of IL1ß and TNFα gene expression in arthritic joints in ...
Figure 7
Predominant TCR Vß6 and Vß8 usage in arthritic joints in B6.IFNγ KO mice. Expression of TCR Vß gene expression was determined by quantitative real-time RT-PCR. This composite graph shows individual arthritic mouse samples ...

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