Human eosinophils regulate T-cell functions through induction of indoleamine 2,3-dioxygenase
Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme in tryptophan catabolism, is inducible by IFNγ, resulting in kynurenine production, which inhibits proliferation and induce apoptosis of Th1 cells; an important mechanism of inhibition of T-cell function by regulatory dendritic cells. Eosinop...
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Published in | Journal of allergy and clinical immunology Vol. 113; no. 2; p. S172 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
St. Louis
Mosby, Inc
01.02.2004
Elsevier Limited |
Online Access | Get full text |
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Summary: | Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme in tryptophan catabolism, is inducible by IFNγ, resulting in kynurenine production, which inhibits proliferation and induce apoptosis of Th1 cells; an important mechanism of inhibition of T-cell function by regulatory dendritic cells. Eosinophils increase during allergen challenge and may interact with T-cells. We hypothesize that the eosinophil-derived IDO plays an immunomodulatory role in the maintenance of Th1-Th2 polarization in allergy.
Eosinophils purified from atopic and non-atopic donors were probed for IDO expression by RT-PCR and Western blotting. KYN was measured to determine IDO enzymatic activity. Peripheral blood lymphocyte apoptosis was measured by annexin V following culture with PHA or IFNγ-treated eosinophils. We investigated IDO expression in lung tissue of allergic patients, and in tissues from a mouse model of allergic inflammation, by immunohistochemistry.
IFNγ-treated eosinophils expressed IDO mRNA and protein, and produced KYN. IL-3, IL-5 and GM-CSF had no effect separately but potentiated IDO induction by IFNγ-treated eosinophils. Eosinophils from atopic but not normal donors, expressed IDO constitutively. Lymphocytes cocultured with IDO-expressing eosinophils underwent apoptosis, which was blocked by the IDO inhibitor, 1-methyl-tryptophan. PHA-induced lymphocyte proliferation was inhibited by eosinophil-derived IDO. We observed extensive infiltration by IDO-expressing eosinophils in lymphoid aggregates from atopic subjects. Additionally, eosinophils were the main IDO-expressing cells found in the lung of OVA-sensitized mouse model of allergic inflammation.
Eosinophils may regulate T-cell function, in vivo, through IDO induction and thus contribute directly to the maintenance of Th1-Th2 polarization seen in asthma. |
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ISSN: | 0091-6749 1097-6825 |
DOI: | 10.1016/j.jaci.2004.01.055 |