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The role of adenosine receptor engagement in murine fetal thymocyte development
Author(s) -
Hamad Mawieh
Publication year - 1999
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1699-0463.1999.tb01489.x
Subject(s) - thymocyte , adenosine receptor , fetus , adenosine , receptor , microbiology and biotechnology , immunology , biology , chemistry , endocrinology , medicine , pregnancy , agonist , genetics , t cell , immune system
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 × 10 5 to 2.2 × 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 μM. 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 μM, 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.