Catecholamines as immunomodulators: a role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development

Auton Neurosci. 2008 Dec 15;144(1-2):1-12. doi: 10.1016/j.autneu.2008.09.003. Epub 2008 Oct 30.

Abstract

In its simplest form, effective T cell-mediated immunity emanates from the expansion of specific T cells activated in response to antigen. In establishing and maintaining the peripheral T-cell pool, the thymus plays a critical role. It does so by providing a microenvironment within which T-cell precursors proliferate, differentiate and undergo selection processes to create a fully functional population of major histocompatibility complex restricted, self-tolerant T cells. The control of the thymic function involves intrathymic, as well as sympathetic nervous and endocrine system signalling. In addition to postganglionic noradrenergic fibres, both thymic lymphoid and non-lymphoid cells, including epithelial cells and macrophages, have been demonstrated to express tyrosine hydroxylase (TH), and suggested to form a local non-neural catecholaminergic cell network. A higher level of noradrenaline has been found in male than in female rat thymi, and a role of gonadal hormones in providing this dimorphism has been demonstrated. In addition, thymic lymphoid and non-lymphoid cells, including those expressing TH, have been found to bear beta- and alpha1-adrenoceptors (ARs) and a role of gonadal hormones in regulation of, at least, beta-AR density and signalling has been suggested. These findings have also entailed conclusion that catecholamines (CAs) influence T-cell development, not only via neurocrine/endocrine, but also via autocrine/paracrine action. Generally, CAs have been shown to exert an inhibitory influence on thymopoiesis. Role of alpha1- and beta-AR-mediated mechanisms in maintaining thymic homeostasis and in fine tuning of both conventional and regulatory T-cell development is discussed in the manuscript.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autocrine Communication / immunology
  • Catecholamines / physiology*
  • Cell Differentiation / immunology
  • Female
  • Humans
  • Immunologic Factors / physiology*
  • Lymphopoiesis / immunology
  • Male
  • Rats
  • Receptors, Adrenergic / physiology*
  • Sex Characteristics
  • T-Lymphocytes / immunology*
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology*
  • Thymus Gland / innervation
  • Tyrosine 3-Monooxygenase / immunology

Substances

  • Catecholamines
  • Immunologic Factors
  • Receptors, Adrenergic
  • Tyrosine 3-Monooxygenase