T cell epitope-specific defects in the immune response to cat allergen in patients with atopic dermatitis.
Atopic dermatitis (AD) is often associated with high titer IgE antibodies (ab) to allergens, and IL-10-mediated regulation of IFN-gamma has been proposed to contribute to this IgE ab production. However, the relevance of IL-10 and IFN-gamma to IgE associated with AD has not been examined in the context of an allergen-specific system. Analysis of PBMC responses in vitro showed deficient T cell proliferation to overlapping IL-10- (peptide (P) 2:1) and IFN-gamma- (P2:2) inducing chain 2 major epitopes of cat allergen (Fel d 1) in cultures from sensitized AD patients (mean IgE to cat=20.9 IU/ml). Diminished IFN-gamma induction by Fel d 1 and P2:2, along with elevated peptide-induced IL-10 (except for P2:1) was observed in PBMC cultures from AD subjects compared with non-AD (sensitized and non-sensitized) subjects. Neither T cell proliferation nor IFN-gamma production to chain 2 epitopes could be restored by anti-IL-10 mAb in cultures from sensitized AD subjects. Moreover, allergen avoidance was associated with a paradoxical decrease in both IL-10 and IFN-gamma in peptide-stimulated PBMC from these subjects. Control of IFN-gamma production to chain 2 epitopes by IL-10 may be relevant to sensitization status. Development of high titer IgE ab in AD could reflect a failure of this mechanism.
Carneiro
Raquel
R
Asthma and Allergic Diseases Center, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908-1355, USA.
Reefer
Amanda
A
Wilson
Barbara
B
Hammer
Juergen
J
Platts-Mills
Thomas
T
Custis
Natalie
N
Woodfolk
Judith
J
D000485:Allergens; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation; D001362:Avoidance Learning; D002415:Cats / Q000276:immunology*; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma; C059296:Fel d 1 protein, Felis domesticus