Costimulation of T‐cell proliferation by anti‐l‐selectin antibody is associated with the reduction of a cdk inhibitor p27

• Published in: Immunology Vol. 116; no. 3; pp. 347 - 353
• Main Authors: Nishijima, Ken‐ichi, Ando, Munetoshi, Sano, Shusuke, Hayashi‐Ozawa, Aiko, Kinoshita, Yoshinori, Iijima, Shinji
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2005; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Animals; Antibodies, Monoclonal - immunology; cdk inhibitor; Cell Proliferation; costimulation; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Interleukin-2 - metabolism; L-Selectin - immunology; Lymph Nodes - immunology; Lymphocyte Activation - immunology; l‐selectin; Male; Mice; Mice, Inbred BALB C; Original; p27; Reverse Transcriptase Polymerase Chain Reaction - methods; Superantigens - immunology; T-Lymphocytes - immunology; T‐cell proliferation
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2005.02234.x

Summary In this study, we investigated the costimulatory activity of l‐selectin in primary mouse T cells. Proliferation induced by immobilized anti‐CD3 antibody was enhanced by immobilized anti‐l‐selectin antibody. In contrast to the anti‐CD28 antibody, anti‐l‐selectin antibody did not enhance interleukin‐2 (IL‐2) expression. One of the cyclin‐dependent kinase (cdk) inhibitors, p27, was reduced by costimulation with anti‐l‐selectin antibody, as with anti‐CD28 antibody, suggesting that the enhancement of T‐cell proliferation is the result of a reduced p27 level. Since anti‐l‐selectin antibody enhanced the activation of extracellular signal‐regulated protein kinase (ERK) induced by anti‐CD3 antibody, ERK plays an important role in signal integration during costimulation. These results suggest that the mechanism of T‐cell costimulation is at least partially different between CD28 and l‐selectin, although the two mechanisms share a common downstream event, a reduction of p27 level, as a critical biochemical event in the cell cycle progression of T cells.