Epitope-specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro.
Open Access
- 1 October 1996
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 98 (7), 1676-1683
- https://doi.org/10.1172/jci118963
Abstract
Bee venom phospholipase A2 (PLA) is the major allergen in bee sting allergy. It displays three peptide and a glycopeptide T cell epitopes, which are recognized by both allergic and non-allergic bee venom sensitized subjects. In this study PLA- and PLA epitope-specific T cell and cytokine responses in PBMC of bee sting allergic patients were investigated before and after 2 mo of rush immunotherapy with whole bee venom. After successful immunotherapy, PLA and T cell epitope peptide-specific T cell proliferation was suppressed. In addition the PLA- and peptide-induced secretion of type 2 (IL-4, IL-5, and IL-13), as well as type 1 (IL-2 and IFN-gamma) cytokines were abolished, whereas tetanus toxoid-induced cytokine production and proliferation remained unchanged. By culturing PBMC with Ag in the presence of IL-2 or IL-15 the specifically tolerized T cell response could be restored with respect to specific proliferation and secretion of the type 1 T cell cytokines, IL-2 and IFN-gamma. In contrast, IL-4, IL-5, and IL-13 remained suppressed. Treatment of tolerized T cells with IL-4 only partially restored proliferation and induced formation of distinct type 2 cytokine pattern. In spite of the allergen-specific tolerance in T cells, in vitro produced anti-PLA IgE and IgG4 Ab and their corresponding serum levels slightly increased during immunotherapy, while the PLA-specific IgE/IgG4 ratio changed in favor of IgG4. These findings indicate that bee venom immunotherapy induces a state of peripheral tolerance in allergen-specific T cells, but not in specific B cells. The state of T cell tolerance and cytokine pattern can be in vitro modulated by the cytokines IL-2, IL-4, and IL-15, suggesting the importance of microenvironmental cytokines leading to success or failure in immunotherapy.This publication has 58 references indexed in Scilit:
- The expanding universe of T-cell subsets: Th1, Th2 and moreImmunology Today, 1996
- Chemiluminescent and Enzyme-Linked Immuno Assays for Sensitive Detection of Human IFN-γJournal of Immunoassay, 1994
- Cloning of a T Cell Growth Factor that Interacts with the β Chain of the Interleukin-2 ReceptorScience, 1994
- Rapid Hymenoptera venom immunotherapy: comparative safety of three protocolsClinical & Experimental Allergy, 1993
- Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic AsthmaThe New England Journal of Medicine, 1992
- Functional subsets of allergen-reactive human CD4+ T cellsImmunology Today, 1991
- The dominant self and the cryptic self: shaping the autoreactive T-cell repertoireImmunology Today, 1991
- Clonal Expansion Versus Functional Clonal Inactivation: A Costimulatory Signalling Pathway Determines the Outcome of T Cell Antigen Receptor OccupancyAnnual Review of Immunology, 1989
- Production of Human Antibodies to Bee Venom Phospholipase A2 in VitroScandinavian Journal of Immunology, 1989
- Generation of Antigen-Specific Suppressor Cells during Allergy DesensitizationThe New England Journal of Medicine, 1980