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Regulation of T-helper cell responses to inhalant allergen during early childhood
journal contributionposted on 1999-09-06, 00:00 authored by C Macaubas, Peter SlyPeter Sly, P Burton, K Tiller, A Yabuhara, B J Holt, T B Smallacombe, G Kendall, M C Jenmalm, P G Holt
Background: Recent evidence suggests that preschool children manifest patterns of allergen-specific skin prick test (SPT) reactivity and in vitro T-cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small sample sizes and a restricted number of cytokines, usually in response to polyclonal stimuli. Objective: To elucidate the relationship between in vivo and in vitro immune responses to a major inhalant allergen house dust mite (HDM) in preschoolers. Methods: Peripheral blood mononuclear cells (PBMCs) from matched groups of HDM-SPT+ and SPT- 6-year-olds (n = 30 and 29, respectively) tested for PBMC responses to HDM, and cytokine production measured at both the protein and mRNA levels. Immunoglobulin (Ig) E and IgG subclass antibody titres were determined in serum. Interrelationships between in vitro and in vivo HDM responses were examined via multivariate analyses. Results: SPT reactivity to HDM was associated with in vitro production by putative T cells of interleukin (IL) -4, IL-5, IL-9, IL-10, IL-13 and low level IFNγ, and with production in vivo of IgE and (all) IgG subclass antibodies; HDM responses in the SPT- group were restricted mainly to IL-10 and IFNγ and very low levels of IL-4; IL-6 production from non-T-cell sources was common. The cytokine most associated with positive SPT responses was IL-9; SPT weal diameter correlated positively with IL-4, IL-5 and IL- 13 and negatively with IL-10. Conclusion: Detailed analysis of cytokine responses in this very young age group have the potential to uncover subtle relationships between in vivo and in vitro allergen reactivity which may be less clear in adults, in whom T-cell response patterns are modified via chronic stimulation. The present findings which suggest potentially important roles for IL-9 and IL-10 in the early phase of allergic disease, may be one such example.