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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

The Tolerant Immune System: Biological Significance and Clinical Implications of T Cell Tolerance

Author(s): Thea Magrone* and Emilio Jirillo

Volume 19, Issue 5, 2019

Page: [580 - 593] Pages: 14

DOI: 10.2174/1871530319666181211161721

Price: $65


Background: T cell tolerance both at thymic and peripheral levels is a mechanism of protection finalized to eradicate autoreactive T cell clones and/or to maintain immune homeostasis, especially, postnatally. Central tolerance occurs in the thymic medulla via a mechanism of negative selection which leads to the eradication of autoreactive T cell clones.

Mechanisms of Action: Such a tolerogenic event relies on Fas-mediated apoptosis of autoreactive T cell clones operated by thymic dendritic cells (DCs), on the one hand. On the other hand, activated thymic T regulatory (Treg) cells in cooperation with medullary thymic epithelial cells and DCs suppress autoreactive T cell clones. Peripherally, different types of Treg cells exert the so-called peripheral tolerance towards autoreactive T cell clones which may have escaped from negative selection mechanisms. At the same time, peripheral Treg cells activated by tolerogenic DC have antiinflammatory activities, especially in the intestine towards food and microbial antigens.

Drug Targeting: Various natural and dietary products, such as vitamins (A, C, D), lactobacilli and polyphenols will be described for their tolerogenic capacity to attenuate the inflammatory pathway, as observed in preclinical and clinical studies.

Keywords: Dendritic cells, immune system, medullary thymic epithelial cells, natural products, thymus, T regulatory cells.

Graphical Abstract
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