Protease inhibitors diminish lymphocyte stimulation in vitro

Lymphocyte stimulation initiates activation of signal transduction pathways presumably enzymatic in nature. The next step includes gene activation and specific protein molecule production. Proteases of different specificity are crucial in enzyme activation: protein cleavage and biologically active molecule production. To elucidate the role of proteases in peripheral blood mononuclear cell (PBMC) activation, the broad specificity inhibitors of thiol (PHMB) and serine (TLCK) proteases have been used in vitro. Both inhibitors diminished the PHA-induced lymphocyte stimulation when applied at the beginning of culture; inhibitory effect was abrogated when inhibitors were introduced to the culture system 4 h later. Exogenous IL-2 abolished inhibition. PHMB activity was reversible whereas TLCK was irreversible. The inhibition of T lymphocyte-enriched proliferation is more distinctive as compared to that of PBMC. It can be concluded that proteases are involved in early events of lymphocyte proliferation and IL-2 production which is responsible for different stages of cell growth.