Chondrocyte antigen expression, immune response and susceptibility to arthritis

The association of HLA-B27 with certain forms of arthritis implies a role f or 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 t ype II collagen gene (COL2A1), Two Escherichia coli beta -galactosidase (be ta -gal)-expressing lines were derived (CIIL73 and CIIL64) as well as two l ines (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 beta -gal, the response in CIIL64 mice was essential ly normal, However, both lines displayed normal proliferative and antibody responses to beta -gal, A reduced CTL response was seen to NP in the CIINP lines in similar to 65% of the animals. In spite of the persistence of T ce ll responses to the transgene antigens in these lines, induction of CTL res ponses alone has so far failed to induce clinical signs of arthritis, Inter estingly, some animals expressing beta -gal were susceptible to arthritis f ollowing challenge with type II collagen alone, whilst their non-TO litterm ates and TG mice from other lines remained unaffected. As beta -gal is expr essed by E. coli, a component of the normal gut flora, this suggests a poss ible role for gut-derived immune responses, We believe these lines could fo rm the basis of a model for studying links between intestinal inflammation and arthritis.