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 specif ic immunological ''memory''; a predominantly Th2-like response potenti ally leading to allergic reactivity, versus apparent ''unresponsivenes s'' if the memory pool is dominated by Th1 cells. The animal model lit erature suggests that potentially life-long dominance of immune respon ses to individual allergens is established at or around the time of fi rst exposure, and involves an antigen-driven T-cell selection process, In humans, this process is likely to occur for most inhalant allergen s, during early childhood. The outcome of these initial responses can be influenced by a variety of factors, including the nature and compet ence of the antigen presenting cells involved, the functional maturity of the CD4+ T-cell population at tbe time of exposure, and the presen ce of inflammatory or infectious stimuli at the level of the airway mu cose, which can effect the cellular and/or cytokine milieu within loca l draining lymph nodes. Recent studies from the animal models addition ally indicate that the cytokine products from allergen-responsive majo r histocompatibility (MHC) class I restricted CD8+ T-cells, and also f rom 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 sel ects against Th2 cells. The key finding from these studies is that the se regulatory mechanism(s) function optimally in the relatively early stages of immune responses, and are considerably less effective in dev iating established (memory) responses, It is argued below that the pot ential exists for exploitation of this information for the development of novel immunoprophylactic strategies to prevent primary allergic se nsitization in humans at a stage when allergen-specific immune respons es are theoretically most susceptible to regulation i.e. during early childhood.