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 A, (PLA), and TF cell epitope-containing PLA peptides were significantly suppressed after 7 ol of treatment. Simultaneously, the production of IL-10 increased during V-SIT, After 28 d of BV-SIT the anergic state was established, Intracytoplasmic cytokine staining of PBMC combined with surface marker detection revealed that HL-IO 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 PEA-specific and total IgE and enhanced the IgG4 formation. Accordingly, increased HL-IO production by SIT causes specific anergy in peripheral T cells, and regulates specific IgE and IgG4 production toward normal IgG4-related immunity.