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.


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


METHODS
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.
Section of Allergy and Immunology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Ebrahim M
EM
Shakir
Dorothy S
DS
Cheung
Mitchell H
MH
Grayson
D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000266:history / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007167:Immunotherapy / Q000266:history* / Q000639:trends; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000485:Allergens; D019138:Antibodies, Blocking; D007073:Immunoglobulin E