Aerosol-induced immunoglobulin (Ig)-E unresponsiveness to ovalbumin does not require CD8+ or T cell receptor (TCR)-gamma/delta+ T cells or interferon (IFN)-gamma in a murine model of allergen sensitization

• Published in: The Journal of experimental medicine Vol. 187; no. 5; pp. 721 - 731
• Main Authors: Seymour, B W, Gershwin, L J, Coffman, R L
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 02.03.1998
• Subjects: Aerosols; Allergens - administration & dosage; Animals; beta 2-Microglobulin - physiology; CD8-Positive T-Lymphocytes - immunology; Cytokines - metabolism; Desensitization, Immunologic; Eosinophils - immunology; Immunoglobulin E - immunology; Immunoglobulin G - immunology; Interferon-gamma - physiology; Lung - immunology; Lymphocyte Depletion; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin - administration & dosage; Receptors, Antigen, T-Cell, gamma-delta - immunology; T-Lymphocyte Subsets - immunology; Th2 Cells - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.187.5.721

Mice exposed for 20 min daily to aerosolized ovalbumin (OVA) for 10 d at concentrations from 1 to 0.01% OVA made greatly reduced immunoglobulin (Ig)-E responses to subsequent immunogenic OVA challenges, given either intraperitoneally or by aerosol. This IgE-specific unresponsiveness lasted for at least four months. However, these aerosol-treated mice were primed for larger OVA-specific IgG1 and IgG2a responses. The specific reduction in IgE responses was not due to preferential induction of a T helper (Th)-1 response as aerosol OVA- primed mice made greatly reduced Th2 and no detectable Th1 response after rechallenge in vitro. Consistent with this, the increase in circulating eosinophils observed in control Th2-primed mice was absent in aerosol OVA-treated animals. Interferon (IFN)-gamma was not required for this unresponsiveness, as IFN-gamma knockout mice and anti-IFN-gamma antibody-treated wild-type mice had greatly reduced levels of IgE similar to wild-type controls. CD8+ T cells played a relatively small role as IgE responses were reduced to about the same extent in beta2 microglobulin-deficient, or in anti-CD8-treated wild-type mice as in normal mice after aerosol OVA treatment. Similarly, T cell receptor (TCR)-gamma/delta T cells were not required for maximal inhibition of the IgE response. These results demonstrate that exposure to inhaled protein antigens can induce a state of unresponsiveness of CD4+ T cells that results in a prolonged loss of IgE and eosinophil responses to subsequent challenges. This T cell unresponsiveness was shown not to require CD8+ or TCR-gamma/delta+ T cells or IFN-gamma.