An IL-2 paradox: blocking CD25 on T cells induces IL-2-driven activation of CD56(bright) NK cells

• Published in: The Journal of immunology (1950) Vol. 185; no. 2; p. 1311
• Main Authors: Martin, Jayne F, Perry, Justin S A, Jakhete, Neha R, Wang, Xiang, Bielekova, Bibiana
• Format: Journal Article
• Language: English
• Published: United States 15.07.2010
• Subjects: Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; CD56 Antigen - immunology; CD56 Antigen - metabolism; Cell Line; Cell Proliferation - drug effects; Cells, Cultured; Cytotoxicity, Immunologic - drug effects; Cytotoxicity, Immunologic - immunology; Daclizumab; Flow Cytometry; Forkhead Transcription Factors - immunology; Forkhead Transcription Factors - metabolism; Humans; Immunoglobulin G - pharmacology; Immunosuppressive Agents - pharmacology; Interleukin-2 - immunology; Interleukin-2 - metabolism; Interleukin-2 - pharmacology; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukin-7 - immunology; Interleukin-7 - metabolism; Interleukin-7 Receptor alpha Subunit - immunology; Interleukin-7 Receptor alpha Subunit - metabolism; K562 Cells; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lewis X Antigen - immunology; Lewis X Antigen - metabolism; Lewis X Antigen - pharmacology; Signal Transduction - drug effects; Signal Transduction - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism

Daclizumab (Dac), an Ab against the IL-2R alpha-chain, inhibits brain inflammation in patients with multiple sclerosis, while expanding CD56(bright) immunoregulatory NK cells in vivo. We hypothesized that this unexpected expansion is paradoxically IL-2 driven; caused by the increased availability of...