Modelling T-cell-Mediated Suppression Dependent on Interactions in Multicellular Conjugates

León, Kalet; Pérez, Rolando; Lage, Agustín; Carneiro, Jorge

doi:10.1006/jtbi.2000.2169

Cited by 65 publications

(112 citation statements)

References 59 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…A generic analysis of the population dynamics of regulatory and target cell populations involved in adoptive transfers of tolerance leads us to a similar conclusion (34). These two complementary lines of evidence indicate that the maintenance and growth of a regulatory population might depend on the target population it regulates.…”

Section: Discussionmentioning

confidence: 59%

“…Therefore, regulatory cells are fully responsive to the IL-2 produced, which is responsible for the growth of target cells. Explicit modeling of the growth kinetics of regulatory and target cell populations using a model described previously (34), demonstrated that these two alternative explanations can easily account for the data (results not shown). The fitting is degenerated and dependent on several parameters, such as inhibitory and stimulatory coefficients, growth rates of regulatory and target cells, etc., which cannot be measured independently.…”

Section: Discussionmentioning

confidence: 87%

“…where The conjugates with a given stoichiometry present in a culture can be counted using a formalism we proposed previously (34). This formalism is valid as long as the cell cultures fulfill the following additional postulates.…”

Section: A Mathematical Model Of In Vitro Proliferative Responses Depmentioning

confidence: 99%

“…We use a general model (34) describing the distribution of multicellular conjugates in a population of regulatory T cells, target T cells, and APCs. We first identify the generic quantitative predictions of the requirement for multicellular conjugates, and then test these predictions on several results of in vitro suppression assays reported in the literature.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Three-Cell Interactions in T Cell-Mediated Suppression? A Mathematical Analysis of Its Quantitative Implications

León

Pérez

Lage

et al. 2001

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Aiming to further our understanding of T cell-mediated suppression, we investigate the plausibility of the hypothesis that regulatory T cells suppress other T cells (target cells), while both cells are conjugated with one APC. We use a mathematical model to analyze the proliferation inhibition scored during in vitro suppression assays. This model is a radical simplification of cell culture reality, assuming that thymidine incorporation is proportional to the number of target cells that would instantaneously form conjugates with APCs that are free of regulatory cells. According to this model the inhibition index should be mainly determined by the number of regulatory cells per APC and should be insensitive to the number of target cells. We reanalyzed several published data sets, confirming this expectation. Furthermore, we demonstrate that the instantaneous inhibition index has an absolute limit as a function of the number of regulatory cells per APC. By calculating this limit we find that the model can explain the data under two non-mutually exclusive conditions. First, only ∼15% of APCs used in the suppression assays form conjugates with T cells. Second, the growth of the regulatory cell population depends on the target cells, such that the number of regulatory cells per APC increases when they are cocultured with target cells and overcomes its limit. However, if neither of these testable conditions is fulfilled, then one could conclude that suppression in vitro does not require the formation of multicellular conjugates.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 87%

Section: A Mathematical Model Of In Vitro Proliferative Responses Depmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Three-Cell Interactions in T Cell-Mediated Suppression? A Mathematical Analysis of Its Quantitative Implications

León

Pérez

Lage

et al. 2001

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similar models were later studied by Borghans et al [17,18] who demonstrated possible onset of autoimmune state, defined as stable above-threshold oscillations in the number of autoreactive cells, as a result of interactions between regulatory and autoreactive T cells. León et al [19][20][21] and Carneiro et al [22] have studied interactions between different T cells, with an emphasis on the suppressing role of regulatory T cells in the dynamics of immune response and control of autoimmunity. Alexander and Wahl [23] have also looked into the role of regulatory T cells, in particular focusing on their interactions with professional APCs and effector cells for the purpose of controlling immune response.…”

Section: Introductionmentioning

confidence: 99%

Effects of Viral and Cytokine Delays on Dynamics of Autoimmunity

Chenar¹,

Kyrychko²,

Blyuss³

2018

Mathematics

View full text Add to dashboard Cite

Abstract:A major contribution to the onset and development of autoimmune disease is known to come from infections. An important practical problem is identifying the precise mechanism by which the breakdown of immune tolerance as a result of immune response to infection leads to autoimmunity. In this paper, we develop a mathematical model of immune response to a viral infection, which includes T cells with different activation thresholds, regulatory T cells (Tregs), and a cytokine mediating immune dynamics. Particular emphasis is made on the role of time delays associated with the processes of infection and mounting the immune response. Stability analysis of various steady states of the model allows us to identify parameter regions associated with different types of immune behaviour, such as, normal clearance of infection, chronic infection, and autoimmune dynamics. Numerical simulations are used to illustrate different dynamical regimes, and to identify basins of attraction of different dynamical states. An important result of the analysis is that not only the parameters of the system, but also the initial level of infection and the initial state of the immune system determine the progress and outcome of the dynamics.

show abstract

Cellular Frustration: A New Conceptual Framework for Understanding Cell-Mediated Immune Responses

Abreu

Nolte-‘Hoen

Almeida

et al. 2006

Lecture Notes in Computer Science

View full text Add to dashboard Cite

Modelling T-cell-Mediated Suppression Dependent on Interactions in Multicellular Conjugates

Cited by 65 publications

References 59 publications

Three-Cell Interactions in T Cell-Mediated Suppression? A Mathematical Analysis of Its Quantitative Implications

Three-Cell Interactions in T Cell-Mediated Suppression? A Mathematical Analysis of Its Quantitative Implications

Effects of Viral and Cytokine Delays on Dynamics of Autoimmunity

Cellular Frustration: A New Conceptual Framework for Understanding Cell-Mediated Immune Responses

Contact Info

Product

Resources

About