Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice

• Published in: The Journal of experimental medicine Vol. 178; no. 5; pp. 1783 - 1788
• Main Authors: HOYNE, G. F, O'HEHIR, R. E, WRAITH, D. C, THOMAS, W. R, LAMB, J. R
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.11.1993; The Rockefeller University Press
• Subjects: Administration, Inhalation; Allergens - administration & dosage; Allergens - pharmacology; Animals; Antibody Formation - drug effects; Antigens, allergens; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Cell Line; Dermatophagoides; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immediate hypersensitivity. Allergy. Anaphylaxis, etc; Immunobiology; Immunosuppression; Mice; Mice, Inbred C57BL; Mites - immunology; Recombinant Proteins - pharmacology; Spleen - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Thymidine - metabolism; Immune response; Antigenic determinant; Peptides; Rodentia; House dust; Acaridida; Cellular immunity; Immunodominance; Dermatophagoides pteronyssinus; Inhalation; Antigen; Acariformes; Arachnida; Vertebrata; Mammalia; Acari; Mouse; Arthropoda; Immune tolerance; T-Lymphocyte; Pyroglyphidae; Invertebrata; Humoral immunity; Allergen
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.178.5.1783

Antigen-specific CD4+ T cells play an important role in the allergic immune response to house dust mite (HDM) allergens in humans. The group 1 allergen of Dermatophagoides spp. is a major target antigen in both B and T cell recognition of HDM. In vitro studies have shown that the presentation of peptides to human T cells under appropriate conditions may lead to a state of specific nonresponsiveness. Therefore, to determine if peptides are able to modulate the function of allergen-reactive T cells in vivo, we have used a murine model of T cell recognition of the HDM allergen Der p 1. The results demonstrate that inhalation of low concentrations of peptide containing the major T cell epitope of Der p 1 (residues 111-139), induces tolerance in naive C57BL/6J mice such that they become profoundly unresponsive to an immunogenic challenge with the intact allergen. When restimulated in vitro with antigen, lymph node T cells isolated from tolerant mice secrete very low levels of interleukin 2, proliferative poorly, and are unable to provide cognate help to stimulate specific antibody production. Furthermore, intranasal peptide therapy was able to inhibit an ongoing immune response to the allergen in mice and this has potential implications in the development of allergen-based immunotherapy.