Autologous mixed lymphocyte responses in experimentally-induced arthritis of the Lewis rat.
Lewis rats develop immune-mediated arthritis following injection with a variety of agents including bovine type II collagen (bCII), mycobacteria, muramyl dipeptide and CP20961. Since susceptibility to experimentally-induced arthritis has been linked to the genes encoding the major histocompatibility complex, it is hypothesized that antigen presentation to autoreactive T-cells is a critical event in the pathogenesis of disease. T-cells, isolated from Lewis rats immunized with bCII or mycobacteria, were co-cultured with splenic or thymic antigen presenting cells (APC) and proliferative responses to antigen were assessed by 3H-thymidine incorporation. T-cell proliferation was observed upon culture with APC without requiring the addition of antigen. T-cells from rats injected with non-immunogenic adjuvants also demonstrated an increased autologous MLR compared to T-cells from non-injected animals. In contrast, T-cells from animals immunized with non-arthritogenic antigens, including ovalbumin or tetanus toxoid, proliferated only when co-cultured with specific antigen-pulsed APC. These results suggest that immunization with arthritogens activates a population of self-reactive T-cells, which respond in an autologous MLR. We propose that these autoreactive T-cells recognize endogenously-derived self peptides rather than peptides derived from a joint autoantigen.
Catchpole
Brian
B
Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, UK. bcatchpo@rvc.ac.uk
Hamblin
Anne S
AS
Staines
Norman A
NA
D000276:Adjuvants, Immunologic; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001168:Arthritis / Q000139:chemically induced* / Q000276:immunology* / Q000382:microbiology; D015551:Autoimmunity / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D007114:Immunization; D007959:Lymphocyte Culture Test, Mixed; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology
D000276:Adjuvants, Immunologic; D000941:Antigens