In CD28-costimulated human naieve CD4+ T cells, I-B kinase controls the expression of cell cycle regulatory proteins via interleukin-2-independent mechanisms

• Published in: Immunology 2010-10, Vol.131 (2), p.231-241
• Main Authors: Lupino, Elisa, Buccinna, Barbara, Ramondetti, Cristina, Lomartire, Annarosa, De Marco, Giovanni, Ricotti, Emanuela, Tovo, Pier-Angelo, Rinaudo, Maria T, Piccinini, Marco
• Format: Article
• Language: English
• ISSN: 0019-2805
• DOI: 10.1111/j.1365-2567.2010.03297.x

SummaryStimulation of naieve CD4+ T cells through engagement of the T-cell receptor (TCR) and the CD28 co-receptor initiates cell proliferation which critically depends on interleukin (IL)-2 secretion and subsequent autocrine signalling via the IL-2 receptor. However, several studies indicate that in CD28-costimulated T cells additional IL-2-independent signals are also required for cell proliferation. In this study, using a neutralizing anti-human IL-2 antibody and two selective, structurally unrelated, cell-permeable I-B kinase (IKK) inhibitors, BMS-345541 and PS-1145, we show that in human naieve CD4+ T cells stimulated through a short engagement of the TCR and the CD28 co-receptor, IKK controls the expression of the cell cycle regulatory proteins cyclin D3, cyclin E and cyclin-dependent kinase 2 (CDK2) and the stability of the F-box protein S-phase kinase-associated protein 2 (SKP2) and its co-factor CDC28 protein kinase regulatory subunit 1B (CKS1B), through IL-2-independent mechanisms.