Clonal Deletion Versus Clonal Anergy: The Role of the Thymus in Inducing Self Tolerance

Abstract

During development in the thymus, T cells are rendered tolerant to self antigens. It is now apparent that thymocytes bearing self-reactive T cell receptors can be tolerized by processes that result in physical elimination (clonal deletion) or functional inactivation (clonal anergy). As these mechanisms have important clinical implications for transplantation and autoimmunity, current investigations are focused on understanding the cellular and molecular interactions that generate these forms of tolerance.

Aging and immunoglobulin isotype patterns in oral tolerance

“…Clonal anergy has been described as operative in the thymus as well as at the periphery (57). Apparently, T cell receptor (TCR) occupancy alone, in the absence of a second costimulatory signal provided by antigen-may partially restore their susceptibility to oral tolerance and, reciprocally, adoptive transfer of cells from old donors to young recipients decreases their susceptibility to tolerance.…”

Augmentation of natural immunity to a pro-inflammatory cytokine (TNF-alpha) by targeted DNA vaccine confers long-lasting resistance to experimental autoimmune encephalomyelitis

“…In the process of negative selection, self-reactive T cells die when they encounter selfantigen in the thymus. 90,91 Similarly, self-specific pre-B cells either die or undergo receptor editing in the bone marrow. 92 It is believed that those cells escaping central tolerance are subjected to various mechanisms acting outside the thymus or the bone marrow to keep them under control.…”

Dendritic cells and tolerance induction

“…Indeed these cells, which are the most effective activators of resting/naive T cells, also appear to regulate the nature of immune responses through the shaping of tolerance induction. The thymus plays a major role in immune homeostasis by the deletion of self-reactive T cells, thus contributing to the maintenance of self-tolerance [44]. A number of cell types present within the thymus may potentially provide signals responsible for the negative selection of developing T cells (reviewed in [45]).…”