Role of interleukin 10 in specific immunotherapy.
The induction of allergen-specific anergy in peripheral T cells represents a key step in specific immunotherapy (SIT). Here we demonstrate that the anergic state results from increased IL-10 production. In bee venom (BV)-SIT the specific proliferative and cytokine responses against the main allergen, the phospholipase A2 (PLA), and T cell epitope-containing PLA peptides were significantly suppressed after 7 d of treatment. Simultaneously, the production of IL-10 increased during BV-SIT. After 28 d of BV-SIT the anergic state was established. Intracytoplasmic cytokine staining of PBMC combined with surface marker detection revealed that IL-10 was produced initially by activated CD4(+)CD25(+), allergen-specific T cells, and followed by B cells and monocytes. Neutralization of IL-10 in PBMC fully reconstituted the specific proliferative and cytokine responses. A similar state of IL-10-associated T cell anergy, as induced in BV-SIT, was found in hyperimmune individuals who recently had received multiple bee stings. The addition of IL-10 to soluble CD40 ligand IL-4-stimulated PBMC or purified B cells inhibited the PLA-specific and total IgE and enhanced the IgG4 formation. Accordingly, increased IL-10 production by SIT causes specific anergy in peripheral T cells, and regulates specific IgE and IgG4 production toward normal IgG4-related immunity.
Akdis
C A
CA
Swiss Institute of Allergy and Asthma Research, CH-7270 Davos, Switzerland. akdisac@isac@siaf.unizh.ch
Blesken
T
T
Akdis
M
M
Wüthrich
B
B
Blaser
K
K
D000328:Adult; D000485:Allergens / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D001514:Bee Venoms / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007167:Immunotherapy; D016753:Interleukin-10 / Q000502:physiology*; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D010741:Phospholipases A / Q000276:immunology; D054467:Phospholipases A2; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D001514:Bee Venoms; D016207:Cytokines; D007074:Immunoglobulin G; D016753:Interleukin-10; D007073:Immunoglobulin E; D010741:Phospholipases A; D054467:Phospholipases A2