T cell activation as starter and motor of rheumatic inflammation

Rheumatic inflammation is driven by sustained specific immunity against self-antigens, resulting in local inflammation and cellular infiltration and, subsequently, in tissue damage. Although the specific autoantigen(s) eliciting the detrimental immune reactions in rheumatic diseases have rarely been defined, it has become clear that the mechanisms resulting in the destruction of tissue and the loss of organ function during the course of the diseases are essentially the same as in protective immunity against invasive microorganisms. Of fundamental importance in initiating, controlling, and driving these specific immune responses are CD4 T cells. Currently available data provide compelling evidence for a major role of CD4 T cells in the initiation and perpetuation of chronic rheumatic inflammation. Consequently, T cell-directed therapies have been employed with substantial clinical success in the treatment of rheumatic diseases. Here, we review current knowledge based on which CD4 T cells can be implicated as the motor of rheumatic inflammation.