Self-organized criticality theory of autoimmunity

Background: The cause of autoimmunity, which is unknown, is investigated from a different angle, i.e., the defect in immune 'system', to explain the cause of autoimmunity. Methodology/Principal Findings: Repeated immunization with antigen causes systemic autoimmunity in mice otherwise not prone to spontaneous autoimmune diseases. Overstimulation of CD4 T cells led to the development of autoantibody-inducing CD4 T (aiCD4 T) cell which had undergone T cell receptor (TCR) revision and was capable of inducing autoantibodies. The aiCD4 T cell was induced by de novo TCR revision but not by cross-reaction, and subsequently overstimulated CD8 T cells, driving them to become antigen-specific cytotoxic T lymphocytes (CTL). These CTLs could be further matured by antigen cross-presentation, after which they caused autoimmune tissue injury akin to systemic lupus erythematosus (SLE). Conclusions/Significance: Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host's immune 'system' by repeated immunization with antigen, to the levels that surass system's self-organized criticality.