Targeting allergen to Fc gammaRI: a strategy to treat allergic disease?

PURPOSE OF REVIEW: Targeting allergens to surface receptors on antigen presenting cells may provide a therapeutic strategy for allergic disease. This article discusses the immunomodulatory capacity of a molecule (H22-Fel d 1), which targets the major cat allergen, Fel d 1, to the high affinity IgG receptor, Fc gammaRI, on human dendritic cells. RECENT
FINDINGS: The fusion protein, H22-Fel d 1, induced a semi-mature phenotype in dendritic cells characterized by production of inflammatory cytokines with no change in surface markers, suggesting tolerogenic capacity. At the T-cell level, H22-Fel d 1 stimulated increased proliferation coupled with amplification of T cells expressing IL-5 and IL-10. Further analysis revealed induction of diverse T cell subtypes characteristic of Th0, regulatory Th1 and regulatory Th2 cells. Notably, this effect was restricted to T cells isolated from cat-allergic patients. Despite the increase in IL-5-expressing T cells, responses induced by H22-Fel d 1 appeared to be regulated by IL-10. Comparison with nonreceptor-targeted allergens from cat and house dust mite confirmed that qualitative T-cell changes induced by H22-Fel d 1 were unique.
SUMMARY: H22-Fel d 1 induces a novel variation of the Th2 response, which incorporates elements of a protective T-cell response. Exploiting Fc gammaRI-mediated pathways for allergen delivery may offer a new approach for treatment.