The Number of Regulatory T Cells: Pursuit of the Golden Mean, pp. 251-268
Authors: (Alexander Pukhalsky, Galina Shmarina, Vladimir Alioshkin, Research Centre for Medical Genetics, Moscow, Russia, and others)
Abstract: Regulatory T cells (Tregs) are an important part of the complex adaptive system of the body that is able to respond to environmental challenges. Tregs maintain peripheral tolerance and play an important role in inflammatory reaction control. Several subsets of Tregs have been described. Naturally occurring CD4+CD25+ Tregs are recognized as a major subset of immune cells maintaining immune self-tolerance in the periphery. Inhibitory potential of these cells against self-reacting T cells is linked to the thymic origin of Tregs. Another subtype of Tregs that is inducible. Such Tregs are generated in the periphery and exert their suppressive potential substantially in the form of anti-inflammatory activity. The latter plays an important role in cooperation of three principal anti-inflammatory mechanisms, which have been developed in the course of evolution: macrophages possessing the suppressive activity (most ancient), Tregs, and stress hormones (phylogenetically youngest). Normally, all three mechanisms of inflammation control are well equalized. However the balance may be disturbed by age due to repeated episodes of stress and HPA axis activation. Consequently, stress hormone release coupled with antigen overload results in Treg accumulation. In time HPA axis activation replaces by its depletion that is manifested by both basal cortisol level decrease and the reduction of stress-induced cortisol response. So, cortisol being in low concentration in the blood is not able any more to control inflammation and Tregs become a principal mechanism of anti-inflammatory machinary. Superfluous Treg accumulation results in development functional somatic syndromes, such as chronic fatigue syndrome, and in some patients, by reason of anticancer immunity suppression, to tumor growth. On the other hand, in childhood the lack of adequate antigen loading may lead to delay of Treg maturation. Allergy and asthma manifestation may be a consequence of such Treg insufficiency. Thus, both excess and deficiency in Treg number may be at the bottom of morbid conditions. The advances in modern pharmacology allow devising the methods of Treg level control.
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