---
_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'
...