
<ArticleTitle>Differential regulation of allergen-specific antibodies in allergy and specific immunotherapy.</ArticleTitle>
<AbstractText>Allergen-specific immunotherapy (SIT) aims to specifically skew an allergic response into a normal immune reaction against an allergen. The response to bee venom (BV) provides an especially suited model to study the immunological mechanisms of SIT in human. The <prot><prot>BV-phospholipase A2</prot> (<prot>PLA</prot>)</prot> represents the major antigen/allergen of BV. In SIT of BV allergy both whole BV and T cell epitope peptides of <prot>PLA</prot> were successfully applied. It appeared that the induction of specific anergy in peripheral T cells and reactivation of the T cells by microenvironmental cytokines represent the basic key steps in the immunological mechanism of SIT. The proliferative and cytokine responses by specific T cells were significantly suppressed simultaneously with an increase in <prot>IL-10</prot> after 7 days. The anergic state was fully established after 4 weeks. Neutralization of <prot>IL-10</prot> in PBMC by a specific antibody reconstituted the original proliferative and cytokine responses. Intracytoplasmatic cytokine staining revealed that <prot>IL-10</prot> was initially produced by activated allergen-specific T cells. <prot>IL-10</prot>-producing B cells and monocytes were involved at a later stage of SIT and in maintenance of the anergy. The addition of <prot>IL-10</prot> to stimulated PBMC or purified B cells inhibited <prot>IgE</prot> synthesis and enhanced the <prot>IgG4</prot> antibody formation. Thus, SIT generates <prot>IL-10</prot>, which in turn induces specific anergy by autokrine interaction in T cells and counter-regulates <prot>IgE</prot> and <prot>IgG4</prot> production. Particular cytokines from the tissue microenvironment reactivate the T cells to produce distinct Th1 or Th2 cytokine patterns respectively and by this way direct SIT towards successful or unsuccessful treatment. High amounts of allergen administered in SIT preferentially generate Th1 cytokines in T cells and <prot>IgG4</prot> antibodies in memory B cells. Further investigations demonstrated that suppression of T cells by <prot>IL-10</prot> is an active process, which depends on the expression and participation of <prot>CD28</prot>.</AbstractText>
