T cell lines generated with type II collagen proliferate in an autologous mixed lymphocyte response.
Collagen-induced arthritis (CIA) is a T cell-dependent disease induced in susceptible rodents by immunizing with bovine type II collagen (bCII). In order to study T cell responses, a programme to generate bCII-specific T cell lines from arthritic rats was initiated. Lymph node cells from bCII-immune WA/KIR/kcl rats were cultured with bCII in vitro, and the T cells were isolated and restimulated with bCII-pulsed antigen presenting cells (APC) (thymus cells or splenic low density cells). However, T cells, generated initially to bCII, subsequently proliferated upon co-culture with syngeneic APC even in the absence of bCII. This suggests that exposure to bCII resulted in the activation of a population of self-reactive T cells which proliferate in an autologous mixed lymphocyte response. In contrast, short-term T cell lines generated to ovalbumin, heat-denatured bCII and the collagen peptide bCII(184-198) proliferated in response to specific antigen-pulsed APC without demonstrating self-reactivity. Since denatured bCII and bCII(184-198) peptide are not arthritogenic and failed to generate self reactivity in vitro, this suggests that the native triple helical conformation of bCII is required for stimulating autoreactive T cell responses.
Catchpole
B
B
Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, London, England. bcatchpo@rvc.ac.uk
Hamblin
A S
AS
Staines
N A
NA
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002417:Cattle; D002460:Cell Line; D018920:Coculture Techniques; D024043:Collagen Type II / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006358:Hot Temperature; D016130:Immunophenotyping; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011489:Protein Denaturation / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D010047:Ovalbumin