Identification of β adrenoceptors during thymocyte ontogeny in mice

Ageing is associated with a progressive decline in thymic cytoarchitecture followed by a less efficient T cell development and decreased emigration of naïve T cells to the periphery. These thymic changes are linked to increased morbidity and mortality from infectious, malignant and autoimmune diseases in old age. Therefore, it is of paramount importance to understand the thymic homeostatic processes across the life span, as well as to identify factors and elucidate mechanisms driving or contributing to the thymic involution. Catecholamines (CAs) derived from sympathetic nerves and produced locally by thymic cells represent an important component of the thymic microenvironment. In young rats, they provide a subtle tonic suppressive influence on T cell development acting via β₂- and α₁-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and thymocytes. In the face of thymic involution, a progressive increase in the thymic noradrenaline level, reflecting a rise in the density of noradrenergic nerve fibers and CA-synthesizing cells, occurs. In addition, the density of β₂- and α₁-AR-expressing thymic nonlymphoid cells and the α₁-AR thymocyte surface density also exhibit a pronounced increase with age. The data obtained from studies investigating effects of AR blockade on T cell development indicated that age-related changes in CA-mediated thymic communications, certainly those involving α₁-ARs, may contribute to diminished thymopoietic efficiency in the elderly. Having in mind thymic plasticity in the course of ageing, and broadening possibilities for pharmacological modulation of CA signaling, we here present and discuss the progress in research related to a role of CAs in thymic homeostasis and age-related decay in the thymic naïve T cell output.

Section: Noradrenergic Innervationmentioning

confidence: 99%

Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity

Leposavić

Pilipović

Perišić

2011

“…Whether the thymus receives cholinergic innervation is still a matter of debate [10,11]. Cholinergic as well as adrenergic receptors were recently detected on thymic lymphocytes [12,13] and epithelial cells [14][15][16]. These findings prompted us to investigate more in depth the possible role of acetylcholine in the regulatory dialogue between thymic lymphocytes and stromal cells.…”

Section: Introductionmentioning

confidence: 99%

A Possible Role for Acetylcholine in the Dialogue between Thymocytes and Thymic Stroma

Rinner

Globerson

Kawashima³

et al. 1999

In this article we will review data suggesting that acetylcholine takes part in the mutual interplay between developing T cells and thymic epithelium, and thereby may influence the generation of the T-cell repertoire. In the first part we will recapitulate our findings according to which cholinergic agonists affect thymocyte apoptosis via a nicotinergic effect on thymic epithelial cells. In the second part we will present evidence that acetylcholine within the thymus is mainly derived from the thymocytes themselves, and that the production and release of this neurotransmitter is dependent on activation of thymic lymphocytes.

“…Having in mind that both thymocytes [25,26,28] and thymic nonlymphoid cells express ß-adrenoceptors [29,30], as well as that adrenergic nerve profiles are localized in close vicinity of these cells [21], it may be supposed that castration, via adrenergic mechanisms, can influence intrathymic T-cell maturation. Additionally, it should be expected that the adrenergic innervation can modulate this process either directly or indirectly, influencing the nonlymphoid cell activity.…”

Section: Discussionmentioning

confidence: 99%

Castration of Sexually Immature Rats Affects Sympathetic Innervation of the Adult Thymus

Leposavić

Ugresic

Pejčić-Karapetrović

et al. 2000

It has been hypothesized that maturational processes within the hypothalamo-pituitary-gonadal (HPG) axis and thymus are reciprocally regulated via neural pathways. To test this hypothesis, in the thymi of adult rats orchidectomized (ORX) at age of 1 (ORX-1), 7 (ORX-7) and 30 days (ORX-30): (i) noradrenaline (NA), dopamine (DA) and serotonin (5-HT) contents and acetylcholinesterase (AChE) activity were measured and (ii) the distribution of monoamine- and AChE-containing nerves and cells was examined by a sucrose phosphate glyoxylic acid (SPG) method and enzyme histochemistry, respectively. In all groups of ORX rats, the thymus weight was significantly increased over that in sham-ORX control rats. In the ORX-1 rats, the increase in the thymus weight was accompanied by a proportional increase in the content of both catecholamines and 5-HT; consequently the concentration of each of them remained unaltered. In these animals, the density of both SPG-stained thymus nerve fibers and cells also remained unchanged. In the ORX-7 rats, the rise in the thymus weight was followed by a proportional increase in the content of all monoamines, except for NA which was reduced. Therefore, in these rats neither the thymus concentrations of DA nor that of 5-HT differed from controls, while the concentration of NA was significantly decreased. The reduction in both NA content and concentration reflected a diminished density of SPG-positive nerve profiles. In the ORX-30 rats, the increase in thymus weight was neither paralleled by a proportional increase in the DA content nor in 5-HT, while the content of NA was decreased. Thus, in their thymi the concentration of both NA and DA, as well as that of 5-HT, were significantly reduced. In parallel with these changes, a decreased density of thymic SPG-positive nerve fibers and cells was found. In all ORX rats, the pattern of intrathymic distribution of SPG-positive fibers and cells remained unchanged. Orchidectomy affected neither the activity of AChE (expressed per gram of tissue) nor the density of AChE-positive nerves and cells in the thymus. As the changes in the density of adrenergic nerve fibers in the thymus from ORX rats were not followed by similar alterations in the density of AChE-containing nerve fibers, it does not seem likely that NA and AChE are colocalized in the thymus nerve fibers. The results also suggest that there is a critical period during ontogenesis when changes within the HPG axis evoked by orchidectomy can affect the sympathetic nerve input to the rat thymus and therefore, most likely, development and function of the organ.