BioModels

Interactions between Macrophages and T-lymphocytes: Tumor
Sneaking Through Intrinsic to Helper T cell Dynamics
ROB J. DE BOER AND PAULINE HOGEWEG
Bioinformatics Group, University of Utrecht, Padualaan 8, 3584 CH Utrecht,
The Netherlands

Abstract

In a mathematical model of the cellular immune response we investigate immune
reactions to tumors that are introduced in various doses. The model represents
macrophage T-lymphocyte interactions that generate cytotoxic macrophages and
cytotoxic T-lymphocytes. In this model antigens (tumors) can induce infinitely large
T-lymphocyte effector populations because (a) effector T-lymphocytes are capable
of repeated proliferation and (b) we have omitted immunosuppression. In this
(proliferative) model small doses of weakly antigenic tumors grow infinitely large
(i.e. sneak through) eliciting an immune response of limited magnitude. Intermediate
doses of the same tumor induce larger immune responses and are hence rejected.
Large doses of the tumor break through, but their progressive growth is accompanied
by a strong immune response involving extensive lymphocyte proliferation. Similarly
a more antigenic tumor is rejected in intermediate doses and breaks through in large
doses. Initially small doses however lead to tumor dormancy. Thus although the
model is devoid of explicit regulatory mechanisms that limit the magnitude of its
response (immunosuppression is such a mechanism), the immune response to large
increasing tumors may either be (a) a stable reaction of limited magnitude (experimentally known as tolerance or unresponsiveness) or (b) a strong and ever increasing
reaction. Unresponsiveness can evolve because in this model net T-lymphocyte
proliferation requires the presence of a minimum number of helper T cells (i.e. a
proliferation threshold). Unresponsiveness is caused by depletion of helper T cell
precursors.