Human T regulatory cell therapy: take a billion or so and call me in the morning.
Immune system regulation is of paramount importance to host survival. In settings of autoimmunity and alloimmunity, control is lost, resulting in injury to vital organs and tissues. Naturally occurring, thymic-derived T regulatory (Treg) cells that express CD4, CD25, and the forkhead box protein 3 (FoxP3) are potent suppressors of these adverse immune responses. Preclinical studies have shown that either freshly isolated or ex vivo expanded Treg cells can prevent both local and systemic organ and tissue destruction. Although promising, human Treg cell infusion therapy has heretofore been difficult to implement in the clinic, and relatively few clinical trials have been initiated. This review will focus on the preclinical models that provide the rationale for current trials and it will address both the challenges and opportunities in human Treg cell therapy.
Riley
James L
JL
Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. rileyj@exchange.upenn.edu
June
Carl H
CH
Blazar
Bruce R
BR
D019264:Adoptive Transfer / Q000009:adverse effects*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D060908:CTLA-4 Antigen; D002469:Cell Separation; D017321:Clinical Trials, Phase I as Topic; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta