Autoimmunity: molecular mimicry or bystander damage

The distinction between pathogen mediated and autoaggressive inflammation is becoming increasingly blurred. Current thoughts on the mechanisms of autoimmune disease broadly fall into two camps, not necessarily mutually exclusive. The molecular mimicry theory holds that tolerant self reactive T cells which have escaped deletion in the thymus generally ignore self antigens mostly as a result of factors such as low affinity of their receptors for antigen, and it is not until they are exposed to antigens from micro-organisms which have homology to self antigens that they receive a sufficiently strong stimulus to be activated. The alternative theory of bystander activation suggests that tissue damage induced by micro-organisms releases a variety of cytokines, not always the same set, which under appropriate circumstances activate self reactive T cells which happen to be in the vicinity as they travel through the tissues. Recently, evidence in support of the latter theory has been reported in a model of experimental diabetes mediated by Coxsackie B infection of pancreatic islet cells (Nature Medicine1998;4:781–5). The requirement for local viral infection was also reported last year in a model of “immune mediated” keratitis, induced by transfer of herpes simplex specific T cells (Science 1998;279:1344–7). The involvement of micro-organisms and especially viruses in putative autoimmune diseases has long been suggested in several ophthalmological conditions, not least the many forms of uveitis, but evidence for viral material in these disorders is particularly …