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PMID: 19281303 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

CD73 is expressed by human regulatory T helper cells and suppresses proinflammatory cytokine production and Helicobacter felis-induced gastritis in mice.

The Journal of infectious diseases ·Vol. 199 ·No. 4 ·2009-02-15 ·Pages 494-504

Alam MS, Kurtz CC, Rowlett RM, Reuter BK, Wiznerowicz E, Das S, Linden J, Crowe SE, Ernst PB

Abstract

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. 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. 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. CD39 and CD73 expressed by Th cells contribute to local accumulation of adenosine and attenuation of gastritis, which may favor persistent infection.

MeSH Terms
5'-Nucleotidase/genetics,metabolism Adenosine/metabolism Animals Antigens, CD/genetics,metabolism Apyrase/genetics,metabolism Cell Proliferation Cells, Cultured Cytokines/genetics,metabolism Flow Cytometry Gastric Mucosa/cytology,immunology Gastritis/genetics,immunology Helicobacter Infections/genetics,immunology,microbiology Helicobacter felis Humans Interferon-gamma/genetics,metabolism Mice Mice, Inbred C57BL Mucous Membrane/cytology,immunology T-Lymphocytes, Helper-Inducer/immunology,metabolism T-Lymphocytes, Regulatory/immunology,metabolism
Chemicals
Antigens, CD Cytokines Interferon-gamma 5'-Nucleotidase Apyrase CD39 antigen Adenosine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Alam Mohammad S
Digestive Health Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA 22908-0708, USA.
Kurtz Courtney C
Rowlett Robert M
Reuter Brian K
Wiznerowicz Elizabeth
Das Soumita
Linden Joel
Crowe Sheila E
Ernst Peter B
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Article Info
Journal
The Journal of infectious diseases
Abbr.
J Infect Dis
ISSN
0022-1899
DOI
10.1086/596205
Published
2009-02-15
Pages
494-504
Language
English
Region
United States
NLM ID
0413675
PMCID
PMC3047419
Subset
IM
Grants
NIAID NIH HHS · R21 AI069880-01 · United States
NIDDK NIH HHS · DK 56703 · United States
NIAID NIH HHS · U01 AI070491-04 · United States
NIDDK NIH HHS · P30 DK067629 · United States
NHLBI NIH HHS · R01 HL037942-20 · United States
NIAID NIH HHS · R21 AI069880 · United States
NIDDK NIH HHS · DK50980 · United States
NIAID NIH HHS · R21 AI069880-02 · United States
NCRR NIH HHS · RR00175 · United States
NIAID NIH HHS · T32 AI007046 · United States
NIAID NIH HHS · U01 AI070491-02 · United States
NHLBI NIH HHS · R01 HL037942 · United States
NIDDK NIH HHS · R01 DK050980-04 · United States
NIAID NIH HHS · R01 AI079145 · United States
NCRR NIH HHS · K26 RR000175 · United States
NIAID NIH HHS · U01 AI070491 · United States
NHLBI NIH HHS · R01 HL037942-23 · United States
NHLBI NIH HHS · R01 HL056111 · United States
NHLBI NIH HHS · R01 HL056111-09 · United States
NIAID NIH HHS · U01 AI070491-03 · United States
NIAID NIH HHS · AI069880 · United States
NIAID NIH HHS · AI70491 · United States
External Links
PubMed source DOI: 10.1086/596205 PMC Full Text View journal details
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