Regulation of IgE and IgG4 responses by allergen specific T-cell clones to bee venom phospholipase A2 in vitro.
An in vitro antibody response to bee venom phospholipase A2 (PLA) from peripheral blood mononuclear cells of bee sting-sensitized individuals was achieved after stimulation with PLA and pokeweed mitogen. This stimulation resulted in a secretion of TH1-associated cytokines and induced PLA-specific and nonspecific IgG4 antibody production but not IgE production. The addition of interleukin-4 (IL-4) to this system decreased the secretion of IgG antibodies, whereas secretion of polyspecific IgE was induced. The mitogen was not required if peripheral blood mononuclear cells were enriched with autologous, PLA-specific, resting T-cell clones in the presence of the antigen. In these experiments the cytokine profile of the particular clone determined the antibody class generated. Low ratios of IL-4 to interferon-gamma, induced by the antigen alone or obtained by neutralizing anti-IL-4 antibodies, enhanced IgG4 antibody formation, whereas IgE levels increased at high ratios of IL-4 to interferon-gamma. These results suggest a complementary regulation of the main isotypes, IgE and IgG4, implicated in allergic and protective hyperimmune responses.
Carballido
J M
JM
Swiss Institute of Allergy and Asthma Research, Davos.
Carballido-Perrig
N
N
Oberli-Schrämmli
A
A
Heusser
C H
CH
Blaser
K
K
D000818:Animals; D001514:Bee Venoms / Q000201:enzymology*; D001516:Bees / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007299:Insect Bites and Stings / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D010741:Phospholipases A / Q000276:immunology*; D054467:Phospholipases A2; D011043:Pokeweed Mitogens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D001514:Bee Venoms; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011043:Pokeweed Mitogens; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010741:Phospholipases A; D054467:Phospholipases A2