Modeling the role of IL-2 in the interplay between CD4+ helper and regulatory T cells: Assessing general dynamical properties

Mathematical Models of the Impact of IL2 Modulation Therapies on T Cell Dynamics

“…Thus in equilibrium, in the absence of treatments, the system will be either in the tolerant or the autoimmune steady state referred above. Such parameter choice is required to explain properly with the model the results of adoptive transfer experiments in mice, where transferring different proportions of CD4 + CD25 − (helper) and CD4 + CD25 + (regulatory) T cells into immune deficient mice (those lacking T cells, Rag −/− or nu −/− ), they either reconstitute a normal (tolerant to self-antigens) immune system or develop an autoimmune disease mediated by the uncontrolled expansion of the transferred auto-reactive CD4 + T cells (28). …”

“…In Ref. (28), three parameter conditions were presented as necessary in the extended model to behave as the original model and therefore to explain the same phenomenology. These conditions are:

Regulatory T cells have to be more efficient using IL-2 at low concentrations than helper and memory T cells.

The existence of a cytokine alternative to IL-2 that promote helper T cell proliferation and survival.

The helper cells must become activated and proliferate more rapidly than Regulatory T cells in conditions of IL-2 excess.

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“…All the interactions involving these T cells occur in the presence of a constant amount of their cognate APCs and relevant homeostatic cytokines. The basic processes and interactions included in the model dynamics for these T cells are (see Figure 2 and (27, 28) for a more detailed biological explanation, including references to experiments that sustained their validity): Resting E and R cells are produced at constant rate by the thymus; they die with a constant decay rate; they get activated (becoming an activated cell) following conjugation to their cognate APCs. The activation of E cells can be inhibited by the presence of co-localized R cells on the APCs.…”

“…The process of conjugation of T cells, on their different functional states, with their cognate APCs is modeled assuming quasi-steady state equilibrium, which leads to the equations presented in Eq. B9 [see a more detailed explanation of the derivation of these equations in (28)]. In Eq.…”

Modeling the T cell immune response: a fascinating challenge

“…However, it was observed that depending on the type of complex used the result could be either expansion of CD8 T cells or Treg [126]. This phenomenon has been explored in models with the aim of developing the best therapeutic strategies for the use of IL-2 to boost Treg and therefore prevent autoimmunity [127,128]. A recent model has also suggested that collective decisions by a population of cells are important in determining whether T cells become activated and that IL-2 availability may be one of the mechanisms by which this is achieved [129].…”