Role of interleukin 10 in specific immunotherapy

J Clin Invest. 1998 Jul 1;102(1):98-106. doi: 10.1172/JCI2250.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology
  • B-Lymphocytes / physiology
  • Bee Venoms / immunology*
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Humans
  • Immune Tolerance
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / classification
  • Immunotherapy*
  • Interleukin-10 / physiology*
  • Middle Aged
  • Monocytes / physiology
  • Phospholipases A / immunology
  • Phospholipases A2
  • T-Lymphocytes / immunology*

Substances

  • Allergens
  • Bee Venoms
  • Cytokines
  • Immunoglobulin G
  • Interleukin-10
  • Immunoglobulin E
  • Phospholipases A
  • Phospholipases A2