Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response in subjects with cat allergy.
BACKGROUND
Induction of CD4+ T cells that produce IL-10 or IFN-gamma is central to the protective effects of conventional allergen immunotherapy.


OBJECTIVE
We examined the T-cell modulatory capacity of a fusion protein (H22-Fel d 1) that targets Fel d 1 to the high-affinity IgG receptor (FcgammaRI) on antigen-presenting cells.


METHODS
Monocyte-derived dendritic cells pulsed with H22-Fel d 1 were analyzed for surface phenotype and cytokine secretion by flow cytometry and cytometric bead assay, respectively. CD4+ T cells generated after coculture with H22-Fel d 1-pulsed dendritic cells were analyzed at the single-cell level by flow cytometry after intracellular cytokine staining. The T-cell repertoire was compared for subjects with (IgE+) and without cat allergy (IgE(neg)IgG(neg)), including subjects with a modified T(H)2 response (IgE(neg)IgG+).


RESULTS
H22-Fel d 1 induced a semimature phenotype in dendritic cells in conjunction with a selective increase in IL-5+ and IL-10+ CD4+ T cells compared with nonreceptor-targeted Fel d 1. Amplified T cells included diverse subtypes characteristic of T(H)0 (IL-5+IFN-gamma+), regulatory T(H)1 (IL-10+IFN-gamma+) and regulatory T(H)2 (IL-10+IL-5+ cells. T-cell qualitative changes were restricted to subjects with allergy and were distinct from a modified T(H)2 response. Blocking IL-10 induced by H22-Fel d 1 selectively increased IL-5+ CD4+ T cells, suggesting that T(H)2 responses were controlled.


CONCLUSIONS
Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response that incorporates major elements of a protective T-cell response.
Hulse
Kathryn E
KE
Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908-1355, USA.
Reefer
Amanda J
AJ
Engelhard
Victor H
VH
Satinover
Shama M
SM
Patrie
James T
JT
Chapman
Martin D
MD
Woodfolk
Judith A
JA
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002415:Cats; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D007073:Immunoglobulin E / Q000097:blood; D017452:Receptors, IgG / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; C489017:FCGR1A protein, human; D006023:Glycoproteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; C059296:Fel d 1 protein, Felis domesticus