--- _id: '2895' abstract: - lang: eng text: One of the fundamental properties of the immune system is its capacity to avoid autoimmune diseases. The mechanism underlying this process, known as self-tolerance, is hitherto unresolved but seems to involve the control of clonal expansion of autoreactive lymphocytes. This article reviews mathematical modeling of self-tolerance, addressing two specific hypotheses. The first hypothesis posits that self-tolerance is mediated by tuning of activation thresholds, which makes autoreactive T lymphocytes reversibly "anergic" and unable to proliferate. The second hypothesis posits that the proliferation of autoreactive T lymphocytes is instead controlled by specific regulatory T lymphocytes. Models representing the population dynamics of autoreactive T lymphocytes according to these two hypotheses were derived. For each model we identified how cell density affects tolerance, and predicted the corresponding phase spaces and bifurcations. We show that the simple induction of proliferative anergy, as modeled here, has a density dependence that is only partially compatible with adoptive transfers of tolerance, and that the models of tolerance mediated by specific regulatory T cells are closer to the observations. acknowledgement: 'The work was financially supported by Fundação para a Ciência e Tecnologia: grants P/BIA/10094/1998, POCTI/36413/99, and POCTI/MGI/46477/2002; and fellowships to JF (Praxis/BCC/18972/98), JS (BD/13546/97), KL (SFRH/BPD+/1157/2002), DM (SFRH/BD/2960/2000) and TP (SFRH/BD/10550/2002).' author: - first_name: Jorge full_name: Carneiro, Jorge last_name: Carneiro - first_name: Tiago full_name: Tiago Paixao id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Dejan full_name: Milutinovic, Dejan last_name: Milutinovic - first_name: João full_name: Sousa, João last_name: Sousa - first_name: Kalet full_name: Leon, Kalet last_name: Leon - first_name: Rui full_name: Gardner, Rui last_name: Gardner - first_name: Jose full_name: Faro, Jose last_name: Faro citation: ama: 'Carneiro J, Paixao T, Milutinovic D, et al. Immunological self tolerance: Lessons from mathematical modeling. Journal of Computational and Applied Mathematics. 2005;184(1):77-100. doi:10.1016/j.cam.2004.10.025' apa: 'Carneiro, J., Paixao, T., Milutinovic, D., Sousa, J., Leon, K., Gardner, R., & Faro, J. (2005). Immunological self tolerance: Lessons from mathematical modeling. Journal of Computational and Applied Mathematics. Elsevier. https://doi.org/10.1016/j.cam.2004.10.025' chicago: 'Carneiro, Jorge, Tiago Paixao, Dejan Milutinovic, João Sousa, Kalet Leon, Rui Gardner, and Jose Faro. “Immunological Self Tolerance: Lessons from Mathematical Modeling.” Journal of Computational and Applied Mathematics. Elsevier, 2005. https://doi.org/10.1016/j.cam.2004.10.025.' ieee: 'J. Carneiro et al., “Immunological self tolerance: Lessons from mathematical modeling,” Journal of Computational and Applied Mathematics, vol. 184, no. 1. Elsevier, pp. 77–100, 2005.' ista: 'Carneiro J, Paixao T, Milutinovic D, Sousa J, Leon K, Gardner R, Faro J. 2005. Immunological self tolerance: Lessons from mathematical modeling. Journal of Computational and Applied Mathematics. 184(1), 77–100.' mla: 'Carneiro, Jorge, et al. “Immunological Self Tolerance: Lessons from Mathematical Modeling.” Journal of Computational and Applied Mathematics, vol. 184, no. 1, Elsevier, 2005, pp. 77–100, doi:10.1016/j.cam.2004.10.025.' short: J. Carneiro, T. Paixao, D. Milutinovic, J. Sousa, K. Leon, R. Gardner, J. Faro, Journal of Computational and Applied Mathematics 184 (2005) 77–100. date_created: 2018-12-11T12:00:12Z date_published: 2005-12-01T00:00:00Z date_updated: 2021-01-12T07:00:32Z day: '01' doi: 10.1016/j.cam.2004.10.025 extern: 1 intvolume: ' 184' issue: '1' month: '12' page: 77 - 100 publication: Journal of Computational and Applied Mathematics publication_status: published publisher: Elsevier publist_id: '3863' quality_controlled: 0 status: public title: 'Immunological self tolerance: Lessons from mathematical modeling' type: journal_article volume: 184 year: '2005' ...