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

C-Q Chu¹, Z Song², L Mayton², B Wu², P H Wooley²

¹ Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
² Department of Orthopaedic Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA

Correspondence to:
Correspondence to:
Dr P H Wooley, Department of Orthopaedic Surgery, Wayne State University, 1 South, Hutzel Hospital, 4707 St Antoine Blvd, Detroit, MI 48201, USA;
ad8754{at}wayne.edu

Background: Transgenic deficiency in interferon (IFN) or IFN receptor makes resistant strains of mice bearing H-2^b or H-2^d 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 IFN knockout C57BL/6 (B6.IFN KO) mice (H-2^b) were compared directly with those in DBA/1 mice (H-2^q).

Results: 60–80% of B6.IFN KO mice developed a progressive arthritis with a similar clinical course to classical CIA in DBA/1 mice. The affected joints in B6.IFN KO mice had an erosive form of arthritis with similar features to joint disease in DBA/1 mice. B6.IFN 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 expression were detected in arthritic joints from ß6.IFN KO and DBA/1 mice. B6.IFNKO 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 IFN production can develop arthritis that resembles classical CIA. These data suggest that IFN is a key factor mediating susceptibility to CIA.

Keywords: collagen induced arthritis; interferon ; T cell receptor

Abbreviations: CFA, complete Freund’s adjuvant; CIA, collagen induced arthritis; CII, collagen type II; IFN, interferon ; IL1ß, interleukin 1ß; KO, knockout; MHC, major histocompatibility complex; MTT, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PBS, phosphate buffered saline; RT-PCR, reverse transcriptase-polymerase chain reaction; TCR, T cell receptor; Th, T helper; TNF, tumour necrosis factor

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