Regulatory T cell adjustment of quorum growth thresholds and the control of local immune responses

• Published in: Journal of theoretical biology Vol. 241; no. 1; pp. 134 - 141
• Main Authors: Burroughs, N.J., Miguel Paz Mendes de Oliveira, Bruno, Adrego Pinto, Alberto
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07-07-2006
• Subjects: Animals; Autoimmunity; Cytokines; Growth model; Immunity, Cellular; Immunology; Interleukin-2 - metabolism; Interleukin-2 - secretion; Lymphocyte Count; Models, Immunological; ODE model; Quorum threshold; Receptors, Interleukin-2 - metabolism; Secretion inhibition; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory - physiology; Tregs; ODE model; Immunology; Growth model; Cytokines; Tregs; Quorum threshold; Secretion inhibition
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2005.11.010

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.