Sharma B
Department of Medicine, University of California, Irvine.
Immunology. 1988 Sep;65(1):101-5.
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.
最近采用膜片钳技术进行的研究表明，人类T淋巴细胞和自然杀伤细胞中存在电压门控性钾通道。本文采用药理学方法，使用电压门控性钾通道电流阻滞剂（4-氨基吡啶、4-AP和四乙铵、TEA）来研究钾通道在细胞毒性细胞前体分化为功能活跃的细胞毒性淋巴细胞过程中的作用。本文所呈现的数据表明，在混合淋巴细胞培养（MLC）中，用CCRF-HSB-2、3163和其他同种异体淋巴细胞激活外周血淋巴细胞5天，可使其对相应靶细胞产生细胞毒性。当向培养物中加入4-AP和TEA（2-4 mM）时，它们以剂量依赖性方式抑制细胞毒性效应细胞的发育。当培养开始时存在4-AP时，细胞毒性淋巴细胞生成受到的抑制最大。然而，当在培养1天后加入4-AP时，几乎没有观察到抑制作用。结果还表明，添加重组白细胞介素-2（rIL-2）以剂量依赖性方式克服了4-AP或TEA介导的细胞毒性淋巴细胞生成抑制。当在第0天或第1天加入外源性IL-2时，4-AP诱导的抑制作用得到最大程度的逆转。综上所述，这些数据表明钾通道在细胞毒性淋巴细胞的生成中发挥作用。
