Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase.
Allergy involves eosinophilia and Th2 polarization. Indoleamine 2,3-dioxygenase (IDO)-catalyzed conversion of tryptophan to kynurenines (KYN) regulates T cell function. We show that human eosinophils constitutively express IDO. Eosinophils treated with IFN-gamma showed an 8-fold increase in IDO mRNA within 4 h; IL-3, IL-5, and GM-CSF had no effect on baseline IDO expression. IL-3 pretreatment of eosinophils reduced IFN-gamma-induced IDO mRNA expression below baseline. Conversely, GM-CSF, but not IL-5, resulted in a 2-fold increase in IFN-gamma-induced IDO. Treatment with IL-3, IL-5, GM-CSF, or IFN-gamma alone expressed IDO enzymatic activity (the presence of KYN in supernatants 48 h postculture). CD28 cross-linking resulted in measurable KYN in culture supernatants, inhibitable by a neutralizing anti-IFN-gamma. Coculture of eosinophils with an IFN-gamma-producing T cell line, but not IL-4-producing T cell clone, led to apoptosis and inhibition of CD3 or CD3/CD28-induced proliferation. Eosinophils infiltrating asthmatic lung and associated lymphoid tissue exhibited intracellular IDO immunoreactivity. Eosinophils may, therefore, maintain Th2 bias through IDO.
Odemuyiwa
Solomon O
SO
Department of Medicine (Pulmonary Research Group), 550A Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Ghahary
Ahmad
A
Li
Yunyuan
Y
Puttagunta
Lakshmi
L
Lee
Joo Eun
JE
Musat-Marcu
Sorin
S
Ghahary
Aziz
A
Moqbel
Redwan
R
D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D004789:Enzyme Activation / Q000276:immunology; D004804:Eosinophils / Q000201:enzymology* / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism / Q000502:physiology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007377:Interleukin-3; D015848:Interleukin-5; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014366:Tryptophan Oxygenase