Publication Date

5-1-2008

Journal

J Immunol. 2008 May 1; 180(9): 6288–6296.

Abstract

After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5'-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. Cd73(-/-) mice have normal sized lymphoid organs in the steady state, but approximately 1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through HEV compared with wild-type mice 24 h after LPS administration. Migration rates of cd73(+/+) and cd73(-/-) lymphocytes into lymph nodes of wild-type mice are equal, suggesting that it is CD73 on HEV that regulates lymphocyte migration into draining lymph nodes. The A(2B) receptor is a likely target of CD73-generated adenosine, because it is the only adenosine receptor expressed on the HEV-like cell line KOP2.16 and it is up-regulated by TNF-alpha. Furthermore, increased lymphocyte migration into draining lymph nodes of cd73(-/-) mice is largely normalized by pretreatment with the selective A(2B) receptor agonist BAY 60-6583. Adenosine receptor signaling to restrict lymphocyte migration across HEV may be an important mechanism to control the magnitude of an inflammatory response.

Keywords

5'-Nucleotidase, Adenosine, Adenosine A2 Receptor Agonists, Adenosine Monophosphate, Aminopyridines, Animals, Cell Movement, Dendritic Cells, Endothelium, Vascular, Inflammation, L-Selectin, Lipopolysaccharides, Lymph Nodes, Mice, Mice, Knockout, Receptor, Adenosine A2B, T-Lymphocytes, Tumor Necrosis Factor-alpha, Up-Regulation, Venules

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