Thymic indoleamine 2,3-dioxygenase-positive eosinophils in young children: potential role in maturation of the naive immune system.
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 ( approximately 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.
Tulic
Meri K
MK
Centre for Child Health Research, University of Western Australia, Perth, Australia.
Sly
Peter D
PD
Andrews
David
D
Crook
Maxine
M
Davoine
Francis
F
Odemuyiwa
Solomon O
SO
Charles
Adrian
A
Hodder
Megan L
ML
Prescott
Susan L
SL
Holt
Patrick G
PG
Moqbel
Redwan
R
D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D007737:Kynurenine / Q000097:blood; D018418:Th2 Cells / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D051193:Toll-Like Receptors; D007737:Kynurenine