Burroughs N J, Miguel Paz Mendes de Oliveira Bruno, Adrego Pinto Alberto
Mathematics Institute, University of Warwick, Coventry CV4 7AL, UK.
J Theor Biol. 2006 Jul 7;241(1):134-41. doi: 10.1016/j.jtbi.2005.11.010. Epub 2006 Jan 5.
The consequences of regulatory T cell (Treg) inhibition of interleukine 2 secretion is examined by mathematical modelling. We demonstrate that cytokine dependent growth exhibits a quorum T cell population threshold that determines if immune responses develop on activation. Secretion inhibition manipulates the growth dynamics and effectively increases the quorum threshold, i.e. to develop immune responses a higher number of T cells need to be activated. Thus Treg induced secretion inhibition can provide a mechanism for tissue specific regulation of the balance between suppression (control) and immune responses, a balance that can be varied at the local tissue level through the regulation of the local active Treg population size. However, nonspecific inhibition is prone to escape of initially controlled autoimmune T cells through cross reactivity to pathogens and bystander proliferation on unrelated immune responses.
通过数学建模研究了调节性T细胞(Treg)抑制白细胞介素2分泌的后果。我们证明,细胞因子依赖性生长表现出一个群体T细胞数量阈值,该阈值决定了免疫反应在激活时是否会发生。分泌抑制会操纵生长动力学,并有效地提高群体阈值,即要产生免疫反应需要激活更多数量的T细胞。因此,Treg诱导的分泌抑制可为组织特异性调节抑制(控制)与免疫反应之间的平衡提供一种机制,这种平衡可通过调节局部活性Treg群体大小在局部组织水平上发生变化。然而,非特异性抑制容易导致最初受控制的自身免疫性T细胞通过与病原体的交叉反应以及在无关免疫反应中的旁观者增殖而逃逸。