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 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.
Leposavić
Gordana
G
Department of Physiology, Faculty of Pharmacy, Belgrade, Serbia. Gordana.Leposavic@pharmacy.bg.ac.yu
Pilipović
Ivan
I
Radojević
Katarina
K
Pesić
Vesna
V
Perisić
Milica
M
Kosec
Dusko
D
D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D002395:Catecholamines / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology*; D038041:Lymphopoiesis / Q000276:immunology; D008297:Male; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development* / Q000276:immunology* / Q000294:innervation; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology
D002395:Catecholamines; D007155:Immunologic Factors; D011941:Receptors, Adrenergic; D014446:Tyrosine 3-Monooxygenase