Thymic indoleamine 2,3-dioxygenase-positive eosinophils in young children: potential role in maturation of the naive immune system

Meri Tulic, Peter Sly, D. Andrews, M. Crook, F. Davoine, S.O. Odemuyiwa, Adrian Charles, Megan Hodder, Susan Prescott, Patrick Holt, R. Moqbel

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Abstract

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.
Original languageEnglish
Pages (from-to)2043-2052
JournalThe American Journal of Pathology
Volume175
Issue number5
DOIs
Publication statusPublished - 2009

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