Feedback mechanisms between T helper cells and macrophages in the determination of the immune response.

The interactions between macrophages and T helper (Th) cells are a complex interplay of positive and negative signals. Some of the mathematical models of interactions between T helpers have indeed taken the influence of macrophages into account. In this work the macrophage is not considered as an extrinsic agent, that is duly directed by the T cells to be cytotoxic, nor is there consideration of T helper cell populations that are dominantly regulated by extrinsic properties of antigens per se, or by certain classes of presenting cells that preferentially select certain classes of lymphocytes or bias their commitment. Rather, a simplified model of feedback loops between Th cells and macrophages is formulated and analyzed. It is suggested how the mutual influence between Th and macrophages can determine the cytokine secretion pattern of these populations. The model provides a feedback scenario to account for experimental findings concerning reversal in the dominance of a specific cytokine profile in the course of some infections. A possible scenario accounting for the difference between the stability of Th1 and Th2 cytokine pattern is put forward. The model suggests explanations for the variability in the outcome of the immune response according to different body compartments. A rationale is presented that accounts for paradoxical findings indicating that Th1 cytokines are sometimes responsible for the downregulation of a Th1 dominated response.