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Originally published online as doi:10.2353/ajpath.2009.090015 on October 8, 2009

Published online before print October 8, 2009
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(American Journal of Pathology. 2009;175:2043-2052.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.090015

Thymic Indoleamine 2,3-Dioxygenase-Positive Eosinophils in Young Children

Potential Role In Maturation of the Naive Immune System

Meri K. Tulic*, Peter D. Sly{dagger}, David Andrews{ddagger}, Maxine Crook§, Francis Davoine, Solomon O. Odemuyiwa, Adrian Charles§, Megan L. Hodder*, Susan L. Prescott*, Patrick G. Holt{dagger} and Redwan Moqbel

From the School of Paediatric and Child Health,* and the Telethon Institute for Child Health Research,{dagger} Centre for Child Health Research, University of Western Australia, Perth, Australia; the Divisions of Cardiac Surgery{ddagger} and Paediatric Pathology,§ PathWest Laboratory Medicine, Princess Margaret Hospital, Perth, Australia; and the Pulmonary Research Group, University of Alberta, Edmonton, Canada

Eosinophils expressing indoleamine 2, 3-dioxygenase (IDO) may contribute to T-helper cell (Th)2 predominance. To characterize human thymus IDO+ eosinophil ontogeny relative to Th2 regulatory gene expression, we processed surgically obtained thymi from 22 children (age: 7 days to 12 years) for immunohistochemistry and molecular analysis, and measured cytokine and kynurenine levels in tissue homogenates. Luna+ eosinophils (~2% of total thymic cells) decreased in number with age (P = 0.02) and were IDO+. Thymic IDO immunoreactivity (P = 0.01) and kynurenine concentration (P = 0.01) decreased with age as well. In addition, constitutively-expressed interleukin (IL)-5 and IL-13 in thymus supernatants was highest in youngest children. Eosinophil numbers correlated positively with expression of the Th2 cytokines IL-5, IL-13 (r = 0.44, P = 0.002), and IL-4 (r = 0.46, P = 0.005), transcription factor signal transducer and activator of transcription-6 (r = 0.68, P = 0.001), and the chemokine receptor, CCR3 (r = 0.17, P = 0.04), but negatively with IL-17 mRNA (r = –0.57, P = 0.02) and toll-like receptor 4 expression (r = –0.74, P = 0.002). Taken together, these results suggest that functional thymic IDO+ eosinophils during human infant life may have an immunomodulatory role in Th2 immune responses.


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