Regulation of T-helper cell responses to inhalant allergen during early childhood

Background Recent evidence suggests that preschool children manifest patter ns of allergen-specific skin prick test (SPT) reactivity and in vitro T-cel l cytokine production which are similar to that of either atopic or nonatop ic adults. However, published studies on this age group involve small sampl e sizes and a restricted number of cytokines, usually in response to polycl onal stimuli. Objective To elucidate the relationship between in viva and in vitro immune responses to a major inhalant allergen house dust mite (HDM) in preschoole rs. Methods Peripheral blood mononuclear cells (PBMCs) from matched groups of H DM-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 det ermined in serum. Interrelationships between in vitro and in vivo HDM respo nses were examined via multivariate analyses. Results SPT reactivity to HDM was associated with in vitro production by pu tative T cells of interleukin (IL)-4, IL-5, IL-9, IL-10, IL-13 and low leve l IFN gamma, and with production in vivo of IgE and (all) IgG subclass anti bodies; HDM responses in the SPT- group were restricted mainly to IL-10 and IFN gamma and very low levels of IL-4; IL-6 production from non-T-cell sou rces was common. The cytokine most associated with positive SPT responses w as 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 g roup 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 fi ndings which suggest potentially important roles for IL-9 and IL-10 in the early phase of allergic disease, may be one such example.