Mechanisms of immunotherapy: a historical perspective.

OBJECTIVE: To provide a historical review of mechanisms proposed during the last century to explain the efficacy of immunotherapy.

DATA SOURCES: We retrieved review articles and original research from MEDLINE, OVID, and PubMed that addressed our topic of interest.

STUDY SELECTION: Articles were selected for their relevance to immunotherapy and mechanisms.

RESULTS: Early studies focused on the production of blocking antibodies induced by immunotherapy, with mechanistic explanations aimed at understanding a relationship between blocking antibodies and clinical response. This was followed by a period when the effects of immunotherapy on levels and function of effector cells in the allergic response were studied. Aiding in characterization of this response was the discovery of IgE and its role in allergic sensitization, which brought a renewed focus on the antibody-mediated effects of immunotherapy. In an attempt to create a unifying hypothesis to explain humoral and cellular mechanisms of immunotherapy, recent approaches have been focused on the role of the T cell and, specifically, regulatory T cells.

CONCLUSIONS: Although the clinical practice of immunotherapy has been refined since its introduction 100 years ago, our understanding of the mechanisms that underlie this success has awaited discoveries in basic immunology.