Abstract
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.
| Original language | English |
|---|---|
| Article number | e8382 |
| Journal | PloS one |
| Volume | 4 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2009 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- General
Cite this
Self-organized criticality theory of autoimmunity. / Tsumiyama, Ken; Miyazaki, Yumi; Shiozawa, Shunichi.
In: PloS one, Vol. 4, No. 12, e8382, 01.12.2009.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Self-organized criticality theory of autoimmunity
AU - Tsumiyama, Ken
AU - Miyazaki, Yumi
AU - Shiozawa, Shunichi
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=77954171663&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0008382
DO - 10.1371/journal.pone.0008382
M3 - Article
C2 - 20046868
AN - SCOPUS:77954171663
VL - 4
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 12
M1 - e8382
ER -