CD73 Is Expressed by Human Regulatory T Helper Cells and Suppresses Proinflammatory Cytokine Production andHelicobacter felis–Induced Gastritis in Mice
Year: 2009
Type: article
Abstract: BACKGROUND: Regulatory T cells (known as "Treg") express apyrases (CD39) and ecto-5'-nucleotidase (CD73) and contribute to their inhibitory function by generating adenosine. We investigated the expression of CD39 and CD73 on human T helper (Th) cells and the role of CD73 in regulating Helicobacter felis-induced gastritis and colonization. METHODS: Human CD4+ Th cells, gastric T cells, or Treg subsets were stimulated and assayed for the expression of CD39 and CD73 by means of reverse-transcriptase polymerase chain reaction and flow cytometry. The effect of CD73 on proliferation and cytokine production was assessed, and the presence of gastritis, proinflammatory cytokine expression, or colonization of H. felis was evaluated in CD73-deficient (CD73-/-) mice or recipient mice given control or CD73-/- Treg. RESULTS: CD4+ T cells expressed CD39 and CD73, particularly in CD25+Foxp3+ Treg from peripheral blood or gastric mucosa. Activation significantly increased CD73 expression on all Th cells. Inhibition of CD73 enhanced production of interferon-gamma. Gastritis in H. felis-infected CD73-/- mice was significantly worse than that in wild-type mice and was accompanied by increased levels of proinflammatory cytokines and reduced bacterial colonization, whereas Treg from CD73-/- mice did not inhibit gastritis. CONCLUSION: CD39 and CD73 expressed by Th cells contribute to local accumulation of adenosine and attenuation of gastritis, which may favor persistent infection.
DOI: 10.1086/596205
Institution: University of Virginia
Language: English
Subfield: Physiology
Domain: Life Sciences
Open Access status: bronze
Funders: Crohn's and Colitis Foundation of America, University of Virginia, Crohn's and Colitis Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1143632765, REGULATION OF AUTOREACTIVE T CELLS IN IL10 KNOCKOUT MICE, G1667163309, G1802781495, The Role of the Adenosine Receptor in Th Cell Development and Function, G296800088, G3985882143, The Novel Role for Adenosine Receptor Agonists in Acquired Neonatal Tolerance, Adenosine Receptor Agonists as an Immunotherapy for Biodefense, Purification & Characterization of Adenosine Receptors, The pathobiology of gastrointestinal disease in mice, UVA Digestive Health Research Center, Infectious Diseases Training Program, Allosteric Enhancement of Adenosine Receptors
OpenAlex ID: W2134616304