Inhibition of the generation of cytotoxic lymphocytes by potassium ion channel blockers.

Recent studies with patch-clamp technique have shown the presence of voltage-gated K+ channels in human T lymphocytes and natural killer cells. Blockers of voltage-gated K+ channel currents (4-Aminopyridine, 4-AP, and tetraethylammonium, TEA), were used here in a pharmacological approach to examine a role of K+ channels in the differentiation of precursors of cytotoxic cells into functionally active cytotoxic lymphocytes. The data presented here demonstrated that activation of peripheral blood lymphocytes with CCRF-HSB-2, 3163 and other allogeneic lymphoid cells for 5 days in mixed lymphocyte culture (MLC) renders them cytotoxic to the respective target cells. Both 4-AP and TEA (2-4 mM), when added to cultures, inhibited the development of cytotoxic effectors in a dose-dependent manner. Maximum inhibition of the generation of cytotoxic lymphocytes occurred when 4-AP was present at the start of cultures. Little or no inhibition was, however, observed when 4-AP was added 1 day of incubation. The results also demonstrate that the addition of recombinant IL-2 (rIL-2) overcame the 4-AP- or TEA-mediated inhibition of the generation of cytotoxic lymphocytes in a dose-dependent manner. The maximum reversal of 4-AP-induced inhibition occurred when exogenous IL-2 was added at Day 0 or 1. Taken together, these data suggest a role of K+ channels in the generation of cytotoxic lymphocytes.