The role of adenosine receptor engagement in murine fetal thymocyte development.
The role of adenosine receptor engagement in murine T-cell development was evaluated by culturing day 15-16 fetal thymic lobes in the presence of various concentrations of the adenosine receptor agonist 5'-(N-ethyl)-carboxamidoadenosine (NECA) or the adenosine receptor antagonist 8-phenyl-theophylline (8-PT) using the fetal thymic organ culture (FTOC) system. Before and 8 days after culture, thymocytes were isolated, counted, and analyzed for the expression of CD4 and CD8 T-cell differentiation molecules. Analysis of fresh thymocytes prior to culture showed that the majority of cells were of the CD4 single-positive or CD4+ CD8+ immature phenotype. Eight days after culture with media alone, 44% of cells were CD4+ and 23% were CD8+, and the number of viable thymocytes had increased from 1.7 x 10(5) to 2.2 x 10(5) cells per thymic lobe. A dose-dependent inhibition of maturation was observed in cultures with 8-PT, with greater than 85% inhibition at 50 microM. The double-positive thymocyte subset was most severely depleted. The number of cells obtained from cultures with NECA was also reduced, with about 65% inhibition at 50 microM, especially the CD8+ subset that was most severely affected. These results suggest that adenosine receptor engagement is required for normal T-cell differentiation and that adenosine receptor agonists and antagonists have distinct effects on thymocyte differentiation. An understanding of the cell-type-specific and developmental expression of adenosine receptors will help elucidate the mechanisms by which adenosine receptor engagement influences T-cell development.
Hamad
M
M
Department of Medical Technology, Zarka Private University, Jordan.
D000241:Adenosine / Q000819:agonists / Q000502:physiology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D009924:Organ Culture Techniques; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D013806:Theophylline; C028322:8-phenyltheophylline; D019204:GTP-Binding Proteins; D000241:Adenosine