Novel aspects of in vitro IL-2 or IFN-α enhanced NK cytotoxicity of healthy individuals based on NKG2D and CD161 NK cell receptor induction

• Published in: Biomedicine & pharmacotherapy Vol. 64; no. 10; pp. 663 - 671
• Main Authors: KONJEVIC, G, MIRJACIC MARTINOVIC, K, VULETIC, A, RADENKOVIC, S
• Format: Journal Article
• Language: English
• Published: Paris Elsevier SAS 01.12.2010; Elsevier
• Subjects: Adult; Biological and medical sciences; Cell Line, Tumor; Cytokines; Cytotoxicity, Immunologic - drug effects; Female; Humans; Interferon-alpha - pharmacology; Interleukin-2 - pharmacology; Internal Medicine; K562 Cells; Killer Cells, Natural - drug effects; Killer Cells, Natural - metabolism; Lymphocytes - drug effects; Lymphocytes - metabolism; Male; Medical Education; Medical sciences; Middle Aged; NK Cell Lectin-Like Receptor Subfamily B - biosynthesis; NK Cell Lectin-Like Receptor Subfamily B - blood; NK Cell Lectin-Like Receptor Subfamily B - genetics; NK Cell Lectin-Like Receptor Subfamily K - biosynthesis; NK Cell Lectin-Like Receptor Subfamily K - blood; NK Cell Lectin-Like Receptor Subfamily K - genetics; NK cell receptors; NK cells; Pharmacology. Drug treatments; Receptors, KIR2DL1 - antagonists & inhibitors; Receptors, KIR2DL1 - genetics; Receptors, KIR2DL3 - antagonists & inhibitors; Receptors, KIR2DL3 - genetics; Receptors, Natural Killer Cell - biosynthesis; Receptors, Natural Killer Cell - blood; Receptors, Natural Killer Cell - genetics; Up-Regulation - genetics; Cytokines; NK cells; NK cell receptors; Healthy subject; Induction; Alpha interferon; NKG2D receptor; Cytokine; Cytotoxicity; In vitro; Natural killer cell; Interleukin 2; T-Lymphocyte; Biological receptor
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2010.06.013

Abstract As IL-2 and IFN-α modulate NK cell activity it was of interest to investigate the expression of newly defined NK cell receptors and augmented NK cell activity in healthy individuals after cytokine in vitro treatment. Peripheral blood lymphocytes (PBL) obtained from 31 healthy volunteers treated for 18 h with 200 IU/ml IL-2 and 250 IU/ml IFN-α were evaluated for NK cell cytotoxicity. Expression of NKG2D, CD161, CD158a, CD158b receptors was analyzed on CD3− CD16+ NK cells, cytotoxic CD16bright and regulatory CD16dim subsets by FACS flow. The found induced significant in vitro enhancement of NK cell activity by both cytokines is supported by specific cytokine induction in PBL of pSTAT1 and pSTAT5, determined by Western blotting, as well as induction of IRF-1 transcription. Both cytokines induce significant up-regulation of NKG2D expression while only IFN-α induced significant up-regulation of CD161, with no alteration in KIR expression by either cytokine on CD3− CD16+ NK cells. Investigated cytokines did not induce change in NK cell bright and dim subset distribution. Moreover, we find that, not only cytokine receptor induction on the CD3− CD16+ NK cells, but also simultaneous increase in their percentage and/or density on CD16bright and CD16dim subsets, represent good indicators of receptor cytokine-susceptibility. As the role of NK cells has been shown in the loss of tolerance, infection and cancer, the data obtained in this study may be of help in NK cell profiling, by giving referent values of cytokine-induced novel NK cell receptor expression either in evaluation of these diseases or in immunomonitoring during cytokine immunotherapy.