Tolerance mechanisms to small molecular compounds

Unbalanced immune responses to small molecular weight compounds lead to a variety of diseases, including allergic contact dermatitis to skin sensitizers and systemic drug hy-persensitivity, both characterized by the uncontrolled ex-pansion of cytotoxic CD8+ and CD4+ T lymphocytes. Evi-dence exists that specialized subsets of T lymphocytes with regulatory function modulate immune responses to chemi-cals by preventing the occurrence of the hypersensitivity re-actions in healthy, non-allergic individuals. In addition, regu-latory mechanisms may have a role in dampening the magnitude of the immune response in allergic subjects to avoid excessive tissue damage. Dendritic cells orchestrate immune responses to chemicals. Depending on their ma-turative state they can expand effector lymphocytes respon-sible for hypersensitivity reactions, or interleukin-10-releas-ing and CD4+CD25+ T lymphocytes, responsible for the establishment of specific tolerance to the potential sensitizer. The understanding of the underlying mechanisms of toler-ance induction is a critical step for the development of ther-apeutical strategies for delayed hypersensitivity reactions.