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　　External Websites Ask the Chatbot a Question Written by Written by Kara Rogers Kara Rogers is the senior editor of biomedical sciences at Encyclopædia Britannica, where she oversees a range of content from medicine and genetics to microorganisms. She joined Britannica in 2006 and... Kara Rogers Fact-checked by Fact-checked by The Editors of Encyclopaedia Britannica Encyclopaedia Britannica's editors oversee subject areas in which they have extensive knowledge, whether from years of experience gained by working on that content or via study for an advanced degree.... The Editors of Encyclopaedia Britannica Last Updated: Oct. 17, 2025 •Article History Table of Contents Table of Contents Ask the Chatbot { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type" : "Question", "name" : " What is peripheral immune tolerance? ", "acceptedAnswer" : { "@type" : "Answer", "text" : "Peripheral immune tolerance is a set of mechanisms that prevent mature immune cells, especially T cells and B cells, from attacking the bodyu2019s own tissues after the cells have left the thymus and bone marrow, which are the central tolerance sites." } } , { "@type" : "Question", "name" : " How does peripheral immune tolerance prevent autoimmunity? ", "acceptedAnswer" : { "@type" : "Answer", "text" : "Peripheral tolerance prevents autoimmunity by maintaining control over self-reactive lymphocytes through complementary processes, such as anergy, suppression by regulatory T cells (Tregs), and deletion through apoptosis (programmed cell death)." } } , { "@type" : "Question", "name" : " What roles do dendritic cells and B cells play in peripheral immune tolerance? ", "acceptedAnswer" : { "@type" : "Answer", "text" : "Dendritic cells can induce tolerance by presenting antigens without costimulatory signals, thereby promoting anergy or Treg differentiation. B cells undergo receptor editing, anergy, or deletion to prevent self-reactive antibody production." } } , { "@type" : "Question", "name" : " Who discovered peripheral immune tolerance and when? ", "acceptedAnswer" : { "@type" : "Answer", "text" : "Peripheral immune tolerance was discovered in the mid-1990s by Japanese immunologist Shimon Sakaguchi." } } , { "@type" : "Question", "name" : " What is the significance of the FOXP3 gene in immune tolerance? ", "acceptedAnswer" : { "@type" : "Answer", "text" : "The FOXP3 gene is linked to immune tolerance via its role as the master regulator of Tregs, wherein it guides and controls Treg development. Mutations in FOXP3 are associated with severe autoimmune disease." } } ] } Top Questions What is peripheral immune tolerance? Peripheral immune tolerance is a set of mechanisms that prevent mature immune cells, especially T cells and B cells, from attacking the body’s own tissues after the cells have left the thymus and bone marrow, which are the central tolerance sites.

　　How does peripheral immune tolerance prevent autoimmunity? Peripheral tolerance prevents autoimmunity by maintaining control over self-reactive lymphocytes through complementary processes, such as anergy, suppression by regulatory T cells (Tregs), and deletion through apoptosis (programmed cell death).

　　What roles do dendritic cells and B cells play in peripheral immune tolerance? Dendritic cells can induce tolerance by presenting antigens without costimulatory signals, thereby promoting anergy or Treg differentiation. B cells undergo receptor editing, anergy, or deletion to prevent self-reactive antibody production.

　　Who discovered peripheral immune tolerance and when? Peripheral immune tolerance was discovered in the mid-1990s by Japanese immunologist Shimon Sakaguchi.

　　What is the significance of the FOXP3 gene in immune tolerance? The FOXP3 gene is linked to immune tolerance via its role as the master regulator of Tregs, wherein it guides and controls Treg development. Mutations in FOXP3 are associated with severe autoimmune disease.

　　peripheral immune tolerance, the set of mechanisms that prevent immune cells—especially T cells and B cells—from attacking the body’s own tissues after the cells have matured and left so-called central tolerance sites—namely, the thymus and bone marrow. By maintaining control over self-reactive lymphocytes that escaped central tolerance, peripheral immune tolerance serves as a critical protective boundary against autoimmunity.

　　In peripheral tissues, immune tolerance is regulated through several complementary processes. Some self-reactive cells become anergic, meaning that they are inactivated and therefore unable to respond to stimulation by antigens (foreign agents). Others are suppressed by regulatory T cells (Tregs), which actively inhibit immune responses through the release of cytokines, such as TGF-β and IL-10, or through direct cell contact. Deletion mechanisms eliminate potentially harmful lymphocytes through apoptosis (programmed cell death). Together these processes ensure that the immune system can defend against foreign pathogens while remaining tolerant of the body’s own cells and molecules.

　　There are various examples of specific immune cell types that contribute to peripheral immune tolerance. Dendritic cells, for instance, depending on the signals they receive, either activate T cells or induce tolerance by presenting antigens without costimulatory signals, thereby promoting anergy or Treg differentiation. Similarly, B cells undergo receptor editing, anergy, or deletion to prevent the production of self-reactive antibodies. Tolerance can occur in different tissues as well, especially those that continually expose the immune system to self-antigens, such as the intestine, lungs, and liver. The gut, for instance, recognizes harmful pathogens, distinguishing them from harmless food proteins or commensal bacteria—a delicate balance mediated by Tregs and tolerogenic dendritic cells.

　　Peripheral immune tolerance was discovered in the mid-1990s, fueled by the identification of Tregs and the characterization of their role in preventing autoimmunity by Japanese immunologist Shimon Sakaguchi. In the early 2000s American biologists Fred Ramsdell and Mary E. Brunkow uncovered a link between a mutation in the gene Foxp3 and a severe autoimmune disorder in mice. They also found that a similar mutation in the human version of that gene, FOXP3, was responsible for an autoimmune disease known as immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX). In 2003 Sakaguchi connected FOXP3 to immune tolerance, showing that it serves as the master regulator of Tregs, guiding their development. Sakaguchi, Ramsdell, and Brunkow shared the 2025 Nobel Prize for Physiology or Medicine for their discoveries relating to peripheral immune tolerance.

　　Kara Rogers