autoimmune disease

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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

(/ai/CD4^+ T) cell which had undergone T cell receptor (TCR) revision

and was capable of inducing autoantibodies. The /ai/CD4^+ 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 surpass system's self-organized

criticality.