tolerization

Tolerization, or the induction of immunological tolerance, is the process by which the immune system becomes nonresponsive to a specific antigen. The goal is to prevent immune-mediated damage caused by autoimmunity, alloreactivity in transplantation, or unwanted reactions to therapeutic agents while preserving general immune function.

Tolerance can arise through central mechanisms, developed during lymphocyte maturation, or peripheral mechanisms that operate after antigen exposure. Central tolerance involves negative selection in the thymus and bone marrow; peripheral tolerance includes anergy, deletion of reactive cells, and suppression by regulatory T cells.

Strategies to induce tolerization include presenting antigen in non-inflammatory contexts to promote regulatory responses, mucosal exposure that leads to oral or nasal tolerance, and the use of tolerogenic dendritic cells or specific cytokine environments (for example, TGF-beta, IL-10). Peptide-based approaches and gene therapy vectors are also explored.

Applications encompass autoimmunity (e.g., long-term tolerance to self-antigens), transplantation tolerance to reduce or prevent graft rejection, and allergy immunotherapy. In gene therapy, tolerization is pursued to prevent immune responses against vectors or encoded proteins.

Challenges include achieving antigen-specific tolerance without generalized immunosuppression, ensuring durability, and translating strategies from models to humans. Safety concerns, patient variability, and monitoring of immune status are active areas of research.