Proteasome activity is required for T lymphocyte aggregation after mitogen activation.

The proteasome is a multicatalytic complex of proteases involved in T lymphocyte proliferation and activation through multiple mechanisms. In this study, we investigated its role in lymphocyte aggregation. We found that blocking proteasome activity by a proteasome-specific inhibitor lactacystin (LAC) prevented clustering of T lymphocytes after stimulation with various mitogens. Expression of adhesion molecules ICAM-1 and LFA-1 at cell surfaces of activated T cells was decreased after treatment with LAC. Mechanisms by which the proteasome intervenes in the expression of these adhesion molecules were different. LAC inhibited ICAM-1 expression at the mRNA level, whereas LFA-1 inhibition was probably at a post-translational level. Downregulation of these molecules after proteasome inhibition likely contributes to the observed repression of T cell aggregation. Our results show that the proteasome plays an important role in cell-cell interaction during T cell activation. Copyright 2001 Wiley-Liss, Inc.