Chondrocyte antigen expression, immune response and susceptibility to arthritis

• Published in: International immunology 2001-04, Vol.13 (4), p.421-429
• Main Authors: Chan, Vera S. F., Cohen, E. Suzanne, Weissensteiner, Thomas, Cheah, Kathryn S. E., Bodmer, Helen C.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; ankylosing spondylitis; Antibodies; Arthritis - etiology; Arthritis - immunology; autoimmunity; BALB/c; beta-Galactosidase - biosynthesis; beta-Galactosidase - immunology; Cartilage, Articular - immunology; CFA Freund's complete adjuvant; Chondrocytes - immunology; CIA collagen-induced arthritis; CII type II collagen; COL2A1 human type II collagen gene; collagen; Collagen - genetics; CSE cartilage-specific element; CTL cytotoxic T lymphocyte; cytotoxic T lymphocyte; Disease Susceptibility; Escherichia coli; Escherichia coli - genetics; Genetic Vectors; histocompatibility antigen HLA; Humans; IFA Freund's incomplete adjuvant; Immunization; influenza A virus; LacZ β-galactosidase gene; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; NP nucleoprotein; nucleoprotein; Nucleoproteins - biosynthesis; Nucleoproteins - immunology; RNA-Binding Proteins; rodent; T-Lymphocytes, Cytotoxic; TG transgenic; tolerance; Viral Core Proteins - biosynthesis; Viral Core Proteins - immunology; β-gal β-galactosidase; β-galactosidase
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/13.4.421

The association of HLA-B27 with certain forms of arthritis implies a role for MHC class I-restricted T cells in the arthritic process. Our aim was to study CD8+ T cell responses towards specific antigens localized in joint tissue. Known determinants were introduced into chondrocytes of transgenic (TG) mice, under the control of the cis-regulatory sequences of the human type II collagen gene (COL2A1). Two Escherichia coli β-galactosidase (β-gal)-expressing lines were derived (CIIL73 and CIIL64) as well as two lines (CIINP) expressing influenza A virus nucleoprotein (NP). Expression of the antigens could be demonstrated in cartilaginous tissues. The TG lines showed variable degrees of responsiveness towards the transgene-introduced antigens; whilst 75% of CIIL73 mice had an impaired cytotoxic T lymphocyte (CTL) response towards β-gal, the response in CIIL64 mice was essentially normal. However, both lines displayed normal proliferative and antibody responses to β-gal. A reduced CTL response was seen to NP in the CIINP lines in ~65% of the animals. In spite of the persistence of T cell responses to the transgene antigens in these lines, induction of CTL responses alone has so far failed to induce clinical signs of arthritis. Interestingly, some animals expressing β-gal were susceptible to arthritis following challenge with type II collagen alone, whilst their non-TG littermates and TG mice from other lines remained unaffected. As β-gal is expressed by E. coli, a component of the normal gut flora, this suggests a possible role for gut-derived immune responses. We believe these lines could form the basis of a model for studying links between intestinal inflammation and arthritis.