On the role of a possible dialogue between cytokine and TCR-presentation mechanisms in the regulation of autoimmune disease

Journal of Theoretical Biology
R L Bar-Or, L A Segel

Abstract

Autoimmune diseases are thought to occur through some weakness in an active process of autoregulation. Two different regulatory mechanisms have been proposed separately during the years: a "non-specific" mechanism, via Th1-Th2 non-specific cytokines, and a "specific" one-on-one mechanism, via presentation of peptides, i.e., T cell receptor (TCR) peptides, by the T cells themselves. Several anti-idiotypic models rely on the latter to explain the effects of "T-cell-vaccination" therapy. We present and analyse a model for the interaction between both regulatory mechanisms within an ensemble composed of Th1 and Th2 cells. Our model shows how both TCR presentation and non-specific Th1/2 signals can cooperate in the choice of the prevailing Th1 or Th2 response. We show how TCR presentation can foster regulation, without necessitating a particular "suppressor" agent, of the type that some have assumed to play a central role in the regulation of autoimmunity. Our results suggest an important role for the cells' sensitivities to Th1 and Th2 derived cytokines; only for certain sensitivity ranges, is it possible to switch dominance between subtypes. It is argued that memory is sustained via modulation of sensitivities to cytokines, not on...Continue Reading

Citations

Sep 9, 2010·PLoS Computational Biology·Aurélien NaldiDenis Thieffry
Nov 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Paola BossùDiana Boraschi
Mar 13, 2014·Bulletin of Mathematical Biology·Seongwon LeeYangjin Kim
Dec 9, 2014·Journal of Theoretical Biology·Robert Root-Bernstein, DeLisa Fairweather
Oct 3, 2000·Journal of Theoretical Biology·A YatesR Callard

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