Interactions at the Dendritic Cell / T-Cell Interface Define the Balance between Immunity and Tolerance

Abstract

Autoimmunity develops when the adaptive immune system reacts against self-antigens, causing destruction or altered function of the host’s own healthy tissues. Although the mechanisms responsible for the loss of tolerance to self have not yet been fully elucidated, it is thought that both genetic predisposition and environmental triggers may be involved. Considering that dendritic cells (DCs) are the antigen- presenting cells (APCs) determining the primary activation of naïve T cells, they play a pivotal role in the regulation of adaptive immunity and the maintenance of immune tolerance to self-antigens. It is thought that T cells recognizing self-constituents in the periphery are kept under control by immature DCs, through the presentation of self-antigens in the absence of costimulation. Thus, alterations in the physiology of DCs could be responsible for incomplete tolerance to self. The main focus of this review will be the capacity of the immunological synapse occurring at the DC/T-cell interface to fine-tune the balance between tolerance and immunity and how alterations on some of the constituents that participate in the synapse can determine induction or perpetuation of undesired immune responses. Factors modulating DC function and thus influencing the course of the adaptive immunity, such as activating/inhibitory receptors expressed on the surface of DCs, and pharmacological approaches will be also discussed.

Current Concepts on Immune Regulation: Impact on Scientific and Clinical Aspects of Immunohematology

“…They describe how alterations of some of the constituents that participate in the synapse can determine induction or perpetuation of undesired immune responses. Physiological factors and pharmacological approaches modulating dendritic cell function and thus influencing the course of the immune response are also discussed [10]. Jan Buer and colleagues, Germany, present an update on mechanisms of central and peripheral T-cell tolerance and focus in particular on the concepts of tolerance mediated by regulatory T cells.…”