Specific immune tolerance of antigen-presenting cells: Hypothesis and significance

Antigen-presenting cells (APCs) play a crucial role in both innate and adaptive immunity. The mechanisms for APCs to distinguish self and nonself have not been uncovered. In the present manuscript, we hypothesized the balance between the activating and inhibiting receptors on APCs will control the state of APCs. In general, they keep balanced by the endogenous ligands so that APCs are in a non-activating state in the naïve bodies. However, foreign antigens or altered self cells will trigger the activating/inhibiting receptors positively or negatively, so these receptor-mediated signals into APCs will be in tendency to be unbalanced. As long as the activating signals are over the inhibiting receptors, APCs will then be activated to function. This hypothesis will help us to explain how APCs can distinguish self and nonself antigens as well as their close relationships with the occurrence of autoimmune diseases. The activated state of APCs in the early stage of autoimmune diseases may be due to imbalance of the activating/inhibiting receptors on APCs triggered by host endogenous ligands. On the other hand, the poor immunity against tumor cells in the late stage of tumor patients may be partially due to the so-called "tolerance" state of APCs in hosts. We believe that, with the proving by the coming evidences, the impacts of the present hypothesis on basic and clinical immunology would be significant.