Immune tolerance

Activated T cells expressing IL-2 receptor a-chains (CD25) (i.e., Regulatory T Cells (Tregs)) maintain immunologic self-tolerance. Among the key mechanisms of Immune tolerance, recent studies have identified that regulatory T cells (Tregs) are crucial in sustaining self-tolerance and immune homeostasis. They achieve this by suppressing a wide range of physiological and pathological immune responses against self, nonself, and quasi-self tumor antigens. The most physiologically relevant Treg population is CD25+ CD4+ Tregs, which naturally occur in the immune system as about 10% of CD4+ T cells and specifically express the transcription factor Foxp3 (forkhead box P3 transcription factor). Regulatory T cells play a crucial role in preventing catastrophic autoimmunity during the entire lifespan of mice.. A deficiency or dysfunction in these cells clearly leads to a breach in self-tolerance, resulting in autoimmune diseases in otherwise normal animals. In humans, mutations in the Foxp3 gene impair the development and function of CD25+ CD4+ Tregs, leading to autoimmune diseases such as type 1 diabetes, severe allergies, and inflammatory bowel disease. This condition, known as immune deficiency, polyendocrinopathy, X-linked (IPEX) syndrome, unequivocally establishes the essential role of naturally occurring Foxp3+ Tregs in maintaining self-tolerance and immune homeostasis. Additionally, evidence is accumulating in both humans and rodents that Foxp3+ CD25+ CD4+ Tregs predominantly infiltrate tumors and seemingly hinder immune responses to tumor cells.

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Sakaguchi et al. 2004 Annu Rev Immunol 22: 531-62
Kim et al. 2007a Nat Immunol 8: 191-7
Lahl et al. 2007 J Exp Med 204: 57-63

see also:
Oral tolerance