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


CONCLUSIONS
CD39 and CD73 expressed by Th cells contribute to local accumulation of adenosine and attenuation of gastritis, which may favor persistent infection.
Alam
Mohammad S
MS
Digestive Health Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA 22908-0708, USA.
Kurtz
Courtney C
CC
Rowlett
Robert M
RM
Reuter
Brian K
BK
Wiznerowicz
Elizabeth
E
Das
Soumita
S
Linden
Joel
J
Crowe
Sheila E
SE
Ernst
Peter B
PB
D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001081:Apyrase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology; D005756:Gastritis / Q000235:genetics / Q000276:immunology*; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D044922:Helicobacter felis; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D007371:Interferon-gamma; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine