Immune privilege induced by regulatory T cells in transplantation tolerance

Abstract

Immune privilege was originally believed to be associated with particular organs, such as the testes, brain, the anterior chamber of the eye, and the placenta, which need to be protected from any excessive inflammatory activity. It is now becoming clear, however, that immune privilege can be acquired locally in many different tissues in response to inflammation, but particularly due to the action of regulatory T cells (Tregs) induced by the deliberate therapeutic manipulation of the immune system toward tolerance. In this review, we consider the interplay between Tregs, dendritic cells, and the graft itself and the resulting local protective mechanisms that are coordinated to maintain the tolerant state. We discuss how both anti-inflammatory cytokines and negative costimulatory interactions can elicit a number of interrelated mechanisms to regulate both T-cell and antigen-presenting cell activity, for example, by catabolism of the amino acids tryptophan and arginine and the induction of hemoxygenase and carbon monoxide. The induction of local immune privilege has implications for the design of therapeutic regimens and the monitoring of the tolerant status of patients being weaned off immunosuppression.

Adaptive TGF-β-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment

“…autoimmunity ͉ immune tolerance ͉ foxP3 ͉ nonobese diabetic mice ͉ CD25 ϩ T cells E vidence has been accumulated to show the essential role of CD4 ϩ T cells expressing CD25 and the foxP3 transcription factor in the maintenance of self-tolerance and in the control of various immune responses (1)(2)(3)(4)(5). Experimental evidence supports the hypothesis that regulatory T cells (Tregs) are delineated into two subsets (6).…”

Infectious tolerance via the consumption of essential amino acids and mTOR signaling

“…ϩ Tregs maintain and transfer tolerance to allografts (3,4). An important component in the maintenance of peripheral tolerance is the ability of Tregs to convert naïve T cells or recent thymic emigrants into further cohorts of Tregs when they encounter antigens presented by the same antigen-presenting cell (APC), usually a dendritic cell (DC), in related phenomena known as linked suppression and infectious tolerance (3,5).…”

“…An important component in the maintenance of peripheral tolerance is the ability of Tregs to convert naïve T cells or recent thymic emigrants into further cohorts of Tregs when they encounter antigens presented by the same antigen-presenting cell (APC), usually a dendritic cell (DC), in related phenomena known as linked suppression and infectious tolerance (3,5). The molecular mechanisms by which Tregs mediate immune regulation and infectious tolerance in vivo remain to be defined, although the expression of TGF-␤ (6), the generation of extracellular adenosine (7), and catabolism of tryptophan (8) have been implicated.…”

Privilege revisited: an evaluation of the eye's defence mechanisms

“…It is even possible to induce immune privilege in certain sites such as in accepted grafts or in tumours, where T regulatory cells are induced by the tissue. 68 In tumours, this form of 'privilege' can be harmful to the organism in the long run by promoting growth of the tumour and metastases. 69 For the eye, many specific tissue-based immunoregulatory mechanisms have been described, most of which disable or deviate the immune response, but some of which can paradoxically promote inflammation (Table 2).…”