Regulatory T-Cell Responses to Low-Dose Interleukin-2 in HCV-Induced Vasculitis

• Published in: The New England journal of medicine Vol. 365; no. 22; pp. 2067 - 2077
• Main Authors: Saadoun, David, Rosenzwajg, Michelle, Joly, Florence, Six, Adrien, Carrat, Fabrice, Thibault, Vincent, Sene, Damien, Cacoub, Patrice, Klatzmann, David
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 01.12.2011
• Subjects: Acquired immune deficiency syndrome; Aged; AIDS; Antiviral agents; Autoimmune diseases; Biological and medical sciences; Biomarkers - analysis; Cancer; CD25 antigen; CD4 antigen; Cell activation; Cryoglobulinemia; Female; Forkhead protein; Foxp3 protein; Gene expression; Gene Expression - drug effects; General aspects; Glucocorticoids; Hepacivirus - genetics; Hepacivirus - isolation & purification; Hepatitis; Hepatitis C; Hepatitis C, Chronic - complications; Humans; Immune system; Immunoregulation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 2; Interleukin-2 - administration & dosage; Interleukin-2 - adverse effects; Interleukin-2 - therapeutic use; Leukocytes (mononuclear); Liver cirrhosis; Lymphocyte Count; Lymphocytes B; Lymphocytes T; Male; Medical sciences; Middle Aged; Monoclonal antibodies; Oxidative stress; Patients; Peripheral blood; Remission Induction; Rituximab; RNA, Viral - blood; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-Lymphocytes, Regulatory - immunology; Targeted cancer therapy; Vasculitis; Vasculitis - drug therapy; Vasculitis - etiology; Viremia; Immune response; Low dose; Cytokine; Cardiovascular disease; Vascular disease; Virus; Medicine; Vasculitis; Interleukin 2; T-Lymphocyte; Flaviviridae; Hepatitis C virus; Hepacivirus; Regulatory cell
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1105143

This phase 1–phase 2a study of the use of low-dose interleukin-2 to treat vasculitis associated with HCV infection suggests the presence of a therapeutic effect that is mediated by an increase in regulatory T cells. Interleukin-2 has been identified for its capacity to stimulate T cells in vitro 1 and has been used to boost effector immune responses in patients with cancers and infectious diseases. 2 , 3 It is a registered indication when used as an adjunct for the treatment of renal-cell carcinoma, but there is a response to treatment in less than 10% of those with the disease, a finding partly explained by the discovery that interleukin-2 mediates the survival and suppressive function of regulatory T cells (Tregs), 4 which are known to suppress antitumor effector responses. 5 , 6 A marked increase in levels of Tregs has been . . .