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

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.