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ESPR EUROPEAN SOCIETY FOR PEDIATRIC RESEARCH: Stockholm, Sweden: September 19–22, 2004

197 Impaired IL-4-Associated Generation of CCR4-Expressing T Cells in Neonates at Hereditary Allergy Risk


Background: Reduced microbial exposure in early life may be partly responsible for an increase in atopic diseases in ‘westernised' societies but the underlying mechanisms remain elusive. Objective To examine how exposure to bacterial lipopolysaccharide (LPS) during the first antigen encounter might influence the maturation of neonatal lymphoid cells, and to analyse possible differences in this respect between neonates with a high risk of allergy due to family history (FH−) and controls with no apparent risk (FH-).

Methods: Cord blood mononuclear cells from the FH+ or FH- group were stimulated with pure LPS or â-lactoglobulin (â-LG) in its inherent LPS milieu. T-cell expression of chemokine receptors CCR4 and CXCR3 was determined by flow cytometry and RT-PCR. Cellular expression of IL-4 was analysed by quantitative RT-PCR, whereas IFN-ã was analysed by both quantitative RT-PCR and ELISA.

Results: Stimulation with LPS, or â-LG together with LPS, induced up-regulation of CCR4 (P<0.05) and CXCR3 (P<0.05). For CCR4 such up-regulation was related to the level of IL-4 produced by the same T cells (rS=0.49, P=0.03), whereas CXCR3 expression was negatively correlated with the IL-4 levels (rS=−0.56, P=0.02). Compared with the FH-group, the FH+ group showed a significantly lower capacity for induction of CCR4+ T cells (mean % of total T cells: FH+, 2.42% vs. FH-, 5.74%; P<0.01), and tended to express less IL-4 mRNA. Conversely, induction of CXCR3 and IFN-ã was not significantly different between the two groups. C

Conclusion: When the immune system in early life encounters antigen together with LPS, T-cell localization for further immune induction within lymphoid tissue is facilitated by CCR4 and CXCR3 expression. In neonates at hereditary risk of allergy this homeostatic mechanism is jeopardised due to poorly up-regulated CCR4. Conversely, Th1 responses to antigen in the presence of LPS is not reduced compared with controls.

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Haddeland, U., Sletten, G., Brandtzaeg, P. et al. 197 Impaired IL-4-Associated Generation of CCR4-Expressing T Cells in Neonates at Hereditary Allergy Risk. Pediatr Res 56, 497 (2004).

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