Autologous Mixed Lymphocyte Responses in Experimentally-induced Arthritis of the Lewis Rat |
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Authors: | Brian Catchpole Anne S Hamblin Norman A Staines |
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Institution: | 1. Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, London, UK;2. Infection and Immunity Research Group, King's College London, University of London, London, UK |
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Abstract: | 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 3 H-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. |
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Keywords: | Antigen Presentation Arthritis Autologous Mlr Autoreactive T-cell |
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