Increased allergen concentration enhances IFN-γ production by allergic donor T cells expressing a peripheral tissue trafficking phenotype

Background: Clinically effective allergen-specific immunotherapy correlates with decreased circulating allergen-specific IL-4(+) T cells but increased IFN-gamma(+) cells at sites of allergen challenge. Whether immunotherapy promotes trafficking of IFN-gamma(+) T cells to peripheral tissues is unknown. As aeroallergen is administered at higher concentrations during immunotherapy than those encountered naturally, the effect of allergen concentration on adhesion molecule (CD62L and CD49d) and chemokine receptor (CCR3 and CCR5) expression by peripheral-blood T cells was analysed in parallel with cytokine production. Methods: House dust mite-allergic donor peripheral blood mononuclear cells were cultured for 14 days with different allergen concentrations. Cytokine profiles of were analysed by flow cytometry. Results: Cultures stimulated with 100 mug/ml house dust mite extract compared with 1 mug/ml had increased proportions and numbers of CD62L(lo), CD49d(hi) or CCR5(+) T cells expressing IFN-gamma. CCR3-positive CD4(+) and CD8(+) T cell numbers were very low and did not differ between cultures. In contrast the proportions of 'peripheral tissue trafficking' CD4(+) T cells expressing IL-4 were decreased in cultures stimulated with high in comparison with low allergen concentration. Conclusion: These results indicate the importance of achieving high allergen doses during immunotherapy to promote IFN-gamma production and expression of a 'peripheral tissue trafficking' phenotype by allergen-specific CD4(+) and CD8(+) T cells. The net change in cytokine milieu at sites of allergen encounter would then down-regulate clinical manifestations of allergic disease.