Immunoregulation of the allergic reaction in the respiratory tract.

The nature of host responsiveness to inhaled antigens is now believed to be a direct reflection of the type of T-cell which dominates specific immunological "memory"; a predominantly Th2-like response potentially leading to allergic reactivity, versus apparent "unresponsiveness" if the memory pool is dominated by Th1 cells. The animal model literature suggests that potentially life-long dominance of immune responses to individual allergens is established at or around the time of first exposure, and involves an antigen-driven T-cell selection process. In humans, this process is likely to occur for most inhalant allergens, during early childhood. The outcome of these initial responses can be influenced by a variety of factors, including the nature and competence of the antigen presenting cells involved, the functional maturity of the CD4+ T-cell population at the time of exposure, and the presence of inflammatory or infectious stimuli at the level of the airway mucosa, which can effect the cellular and/or cytokine milieu within local draining lymph nodes. Recent studies from the animal models additionally indicate that the cytokine products from allergen-responsive major histocompatibility (MHC) class I restricted CD8+ T-cells, and also from allergen-responsive T-cell receptor 1 (TcR1) (gamma/delta) T-cells, play an important role in shaping emerging CD4 T-cell responses, via the creation of an interferon-gamma (IFN-gamma)-rich milieu which selects against Th2 cells. The key finding from these studies is that these regulatory mechanism(s) function optimally in the relatively early stages of immune responses, and are considerably less effective in deviating established (memory) responses. It is argued below that the potential exists for exploitation of this information for the development of novel immunoprophylactic strategies to prevent primary allergic sensitization in humans at a stage when allergen-specific immune responses are theoretically most susceptible to regulation i.e. during early childhood.