Expression of alpha1-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis.
The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCRalphabeta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCRalphabeta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCRalphabeta(high) thymocytes. In urapidil-administered rats the percentage of CD4+CD8- SP TCRalphabeta(high) thymocytes was increased, while that of the CD4-CD8+ TCRalphabeta(high) was reduced, compared with controls. In addition, proportions of CD4+CD25+RT6.1- and CD161+TCRalphabeta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development.
Pesić
V
V
Department of Physiology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
Kosec
D
D
Radojević
K
K
Pilipović
I
I
Perisić
M
M
Vidić-Danković
B
B
Leposavić
G
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015704:CD4 Antigens / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000032:analysis; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018800:Thy-1 Antigens / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D018800:Thy-1 Antigens; C015568:urapidil