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


RESULTS
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.


CONCLUSIONS
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.
Hulse
Kathryn E
KE
Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Woodfolk
Judith A
JA
D000485:Allergens / Q000378:metabolism*; D000818:Animals; D002415:Cats; D003713:Dendritic Cells / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology
D000485:Allergens; D006023:Glycoproteins; D007155:Immunologic Factors; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; C059296:Fel d 1 protein, Felis domesticus