An insight into the early mechanisms of allergen-specific immunotherapy

The mechanisms governing the induction of peripheral tolerance as a result of specific immunotherapy are far from being clearly characterized. In the last 15 years, a number of studies have highlighted the tolerogenic role of regulatory T cells, blocking antibodies and anti-inflammatory cytokines such as IL-10 and TGF-β; however, the best part of our knowledge is mostly limited to mechanisms underlying the maintenance phase. By contrast, little is known regarding the very early effects seen in rush and ultrarush immunotherapy protocols. In this article, Bussmann et al. provide evidence on the possible role, first, of inhibitory receptors of the leukocyte immunoglobulin-like receptor family and, second, of the upregulation of indoleamine 2,3-dioxygenase and subsequent tryptophan starvation on the induction of specific tolerance within a few hours after the initial doses. They also suggest that the observed changes reflect the activation of protective mechanisms, which we are just beginning to understand.