Self-Organized Criticality Theory of Autoimmuity

Ken Tsumiyama1, Yumi Miyazaki1, Shunichi Shiozawa1,2,3,4*

1 Department of Biophysics, Kobe University Graduate School of Health Science, Kobe, Japan, 2 Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan, 3 The Center for Rheumatic Diseases, Kobe University Hospital, Kobe, Japan, 4 Global Center of Excellence (GCOE), Tokyo, Japan



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).


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.

Citation: Tsumiyama K, Miyazaki Y, Shiozawa S (2009) Self-Organized Criticality Theory of Autoimmunity. PLoS ONE 4(12): e8382. doi:10.1371/journal.pone.0008382

Editor: Derya Unutmaz, New York University, United States of America

Received: September 11, 2009; Accepted: November 30, 2009; Published: December 31, 2009

Copyright: © 2009 Tsumiyama et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work is supported by the Global Center of Excellence (GCOE) Program grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Japan Science and Technology Organization. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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