Interleukin-2 and Regulatory T Cells in Graft-versus-Host Disease

• Published in: The New England journal of medicine Vol. 365; no. 22; pp. 2055 - 2066
• Main Authors: Koreth, John, Matsuoka, Ken-ichi, Kim, Haesook T, McDonough, Sean M, Bindra, Bhavjot, Alyea, Edwin P, Armand, Philippe, Cutler, Corey, Ho, Vincent T, Treister, Nathaniel S, Bienfang, Don C, Prasad, Sashank, Tzachanis, Dmitrios, Joyce, Robin M, Avigan, David E, Antin, Joseph H, Ritz, Jerome, Soiffer, Robert J
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 01.12.2011
• Subjects: Adult; Aged; Autografts; Biological and medical sciences; Cancer; CD4 antigen; Cell survival; Chronic Disease; Cohort Studies; Cytokines; Disease Progression; Dose-Response Relationship, Drug; Drug Resistance; Female; Forkhead protein; Forkhead Transcription Factors - metabolism; Foxp3 protein; General aspects; Glucocorticoids; Glucocorticoids - therapeutic use; Graft versus host disease; Graft vs Host Disease - drug therapy; Graft vs Host Disease - immunology; Graft-versus-host reaction; Humans; Immunology; Immunoregulation; Inflammatory diseases; Interleukin 2; Interleukin-2 - administration & dosage; Interleukin-2 - adverse effects; Leukocyte Count; Lymphocytes T; Male; Medical sciences; Middle Aged; Mortality; Observation; T-Lymphocytes, Regulatory - immunology; Young Adult; Medicine; Immunopathology; Graft versus host disease; Interleukin 2; Stem cell; Cytokine; T-Lymphocyte; Hematopoietic cell; Homograft; Graft; Regulatory cell
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1108188

A low daily dose of subcutaneous interleukin-2 increases the number and function of regulatory T cells and results in substantial improvement in about half of patients with chronic graft-versus-host disease. Allogeneic hematopoietic stem-cell transplantation (HSCT) invokes donor-derived immune responses that can result in therapeutic graft-versus-tumor activity and toxic graft-versus-host disease (GVHD). Chronic GVHD, a systemic inflammatory disorder with pleomorphic autoimmune manifestations that is associated with considerable morbidity and mortality, develops in more than half of patients who have undergone HSCT. 1 – 3 Treatment with systemic glucocorticoids has limited efficacy and substantial long-term toxicity. There is no established second-line therapy. Regulatory T (Treg) cells — as defined by expression of CD4, CD25, and transcription factor forkhead box P3 (FOXP3) — account for approximately 5 to 10% of circulating CD4+ T cells, suppress . . .