Chondrocyte antigen expression, immune response and susceptibility to arthritis.
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 beta-galactosidase (beta-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 beta-gal, the response in CIIL64 mice was essentially 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 approximately 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 beta-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 beta-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.
The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, UK.
V S
VS
Chan
E S
ES
Cohen
T
T
Weissensteiner
K S
KS
Cheah
H C
HC
Bodmer
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D001168:Arthritis / Q000209:etiology / Q000276:immunology*; D002358:Cartilage, Articular / Q000276:immunology*; D019902:Chondrocytes / Q000276:immunology*; D003094:Collagen / Q000235:genetics; D004198:Disease Susceptibility; D004926:Escherichia coli / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000276:immunology; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000276:immunology; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000276:immunology
D000906:Antibodies; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D003094:Collagen; D001616:beta-Galactosidase