Qualitative evaluation of adjuvant activities and its application to Th2/17 diseases

Dendritic cells (DCs) are antigen-presenting cells specialized to activate naive T lymphocytes and initiate primary immune responses. The different classes of specific immune responses are driven by the biased development of antigen-specific helper T cell subsets - that is, Th1, Th2, and Th17 cells - that activate different components of cellular and humoral immunity. DCs reside in an immature state in many nonlymphoid tissues such as the skin or airway mucosa which are highly exposed to allergens, pathogens, and chemicals. T cell receptor stimulation with costimulation allows naive Th cells to develop into effector cells, normally accompanied by high-level expression of selective sets of cytokines. The balance of these cytokines and the resulting class of immune responses depend on the conditions under which DCs are primed. Immunomodulators such as lipopolysaccharides/forskolin/curdlan change the nature of DCs to induce Th1/Th2/Th17 cells thereby designated Th1/Th2/Th17 adjuvants. We have recently found that such activities can be scrutinized by using mixed lymphocyte reaction, cAMP, and differential expression of Notch ligand isoforms. Application of these methods for the analyses of atopic dermatitis and experimental autoimmune encephalomyelitis will be discussed.