ROLE OF T-CELLS IN THE DEVELOPMENT OF ARTHRITIS

1. Arthritis can be induced in rodents by priming T-cells to respond t o a foreign antigen and then challenging with antigen intra-articularl y. This may be a model of the situation in human reactive arthritis in which T-cell responses are induced by antigens from organisms which t rigger reactive arthritis (e.g. Chlamydia trachomatis) and antigen fin ds its way to the joint, most probably within macrophages. Priming by previous exposure to antigens similar to those of the triggering organ ism could also play a part in pathogenesis. Genetic factors determinin g the nature and control of the immune response affect the severity an d duration of the arthritis. 2. T-cell-dependent arthritis can be indu ced in rodents by immunization with an antigen known to be expressed i n the joint (e.g. Type II collagen). Whether this is an important mech anism in human arthritis is still unclear, even though diseases such a s rheumatoid arthritis are conventionally thought of as 'autoimmune'. No convincing candidate autoantigen has yet been identified in rheumat oid arthritis, and recent experiments in transgenic mice indicate that arthritis can be induced by an autoimmune T-cell response which does not target an antigen confined to the joint. 3. Adjuvant arthritis is a classical T-cell-dependent animal model of human arthritis; recently arthritis has been described as a rare complication in patients recei ving adjuvant (intra-vesical live BCG organ isms) for blad der cancer. Increasing attention is being paid to the role of adjuvants as 'dange r signals', which allow the immune system to determine whether an anti genic challenge poses a threat. Inappropriate attachment of danger sig nals to self antigens may result in T-cell-mediated immune responses, which could play a part in the pathogenesis of arthritis. 4. Animal st ud ies indicate that autoimmune/inflammatory diseases can be produced by im balances within T-cell populations, and that certain T-cells als o have the capacity to regulate inflammatory responses. Among the latt er are T-cells specific for conserved epitopes within heat shock prote in 60. The extent to which T-cells of this kind operate in human disea se has yet to be determined.