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Over-stimulation of host immune system induces systemic autoimmunity

natasa778

Senior Member
Messages
1,774
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008382
In a perfectly reproducible experiments in which the mice not prone to autoimmune diseases were immunized repeatedly with antigen, we have unexpectedly and surprisingly discovered that overstimulation of immune system beyond its self-organized criticality inevitably leads to systemic autoimmunity. Subsequent detailed molecular analyses revealed in the first that autoantibodies are induced not by cross reaction to antigen but by de novo T cell receptor (TCR) revision. Second, final maturation of effector cytotoxic T lymphocyte (CTL) via antigen cross-presentation is sine qua non for generating autoimmune tissue injury. Most importantly, we now show that autoimmunity arises not from ‘autoimmunity’, but as a natural consequence of normal immune response when stimulated maximally beyond system's self-organized criticality.


These findings indicate that repeated immunization with conventional antigen can induce the generation of aiCD4+ T cells which have undergone TCR revision and are capable of stimulating B cells [9]. This observation is in line with previous findings showing that such somatic mutations occur often in lymphocytes, a process which is considered to be a major stochastic element in the pathogenesis of autoimmunity [10], [11]. Thus, overstimulation of CD4+ T cells by repeated immunization with antigen and induction of full maturation inevitably leads to the generation of aiCD4+ T cells which have undergone TCR revision and are capable of inducing autoantibodies. Importantly, the present study shows that such aiCD4+ T cells are induced by de novo TCR revision but not by cross-reaction to antigen.


... We therefore conclude that systemic autoimmunity necessarily takes place when host's immune ‘system’ is overstimulated by external disturbance, i.e., repeated exposure to antigen, to the levels that surpass system's self-organized criticality, and propose here ‘self-organized criticality theory’ explaining the cause of autoimmunity.
 
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Helen

Senior Member
Messages
2,243
@natasa778 Thanks. Maybe you should post this also in the linked thread, and eventually Professor Edwards will give his comments?

Invest in ME/Prof Jonathan Edwards statement on UK Rituximab trial, 30 July


 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Maybe you should post this also in the linked thread, and eventually Professor Edwards will give his comments?
Invest in ME/Prof Jonathan Edwards statement on UK Rituximab trial, 30 July
Great idea. I think it would be interesting to bring this to Prof Edwards' attention and to ask for his views on it.
@natasa778, would you like to post the info on the other thread, or would you be happy for someone else to post it?
http://forums.phoenixrising.me/inde...tatement-on-uk-rituximab-trial-30-july.24499/