A dynamical perspective of CTL cross-priming and regulation: implications for cancer immunology

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Cytotoxic T lymphocyte (CTL) responses are a major component of the immune system which can remove infected cells and tumour cells and can also inhibit viral replication by non-lytic means. However, the mechanism by which CTL becomes induced is not clear. Recently, studies have been focussed on cross-priming and cross-presentation. In these processes antigen presenting cells (APCs) take up antigen and display it on their surface. The antigen is then recognised by the CTL and this, in turn, leads to their activation. This process of cross-presentation is thought to play a role in regulating the response of the CTL, such as whether the CTL should expand and react, or whether they should enter a state of tolerance. It is thought that a better understanding of these mechanisms will be important for understanding issues such as: why CTL generally do not successfully remove tumours; how CTL tolerance is maintained; and why CTL effectively remove some viral infections but not others.

In the study described here, Wodarz and Jansen develop a mathematical model to suggest and explain a new mechanism in which a dynamical interplay between cross-presentation and direct presentation (where CTL recognise the antigen on the target cell itself) regulates CTL responses. The authors assume that cross-presentation by APCs results in the activation and expansion of CTL. The CTL are then assumed to be exposed to direct presentation on the target cells, which results in lysis of the target cells (see the figure below for more details of the model).

The complete original paper reference is cited below:

A dynamical perspective of CTL cross-priming and regulation: implications for cancer immunology, Dominik Wodarz and Vincent A. A. Jansen, 2003, Immunology Letters , 86, 213-227. (Full text (HTML) and PDF versions of the article are available on the Immunology Letters website.) PubMed ID: 12706524

A schematic diagram of the processes described by the mathematical model. The model contains four variables: T, which represents the target cells which are directly displaying antigen, such as infected cells or tumour cells; A, which denotes non-activated antigen presenting cells (APCs); A*, which represents the loaded and activated APCs which have taken up the antigen and display it; and CTL, which represent cytotoxic T lymphocytes.

Using this model Wodarz and Jansen found that the ratio of cross-presentation to direct presentation can be a deciding factor which determines whether exposure to antigen results in an immune response or tolerance. Higher ratios tend to correlate with the CTL expanding and reacting, while lower ratios are associated with tolerance. The model is applied to study the role of CTL in cancer initiation, cancer evolution/progression, and therapeutic vaccination against cancers.