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

In its simplest form, effective T cell-mediated immunity emanates from the expansion of specific T cells activated tit 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 demo nstrated 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 ill 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 alpha(1)-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 catecholamiens (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 alpha(1)- and beta-R-mediated mechanisms in maintaining thymic homeostasis and in fine tuning of both conventional and regulatory T-cell development is discussed in the Manuscript. (C) 2008 Elsevier B.V. All rights reserved.