Spaggiari G M, Carosio R, Pende D, Marcenaro S, Rivera P, Zocchi M R, Moretta L, Poggi A
Laboratory of Immunology, National Cancer Research Institute, Genova, Italy.
Eur J Immunol. 2001 Jun;31(6):1656-65. doi: 10.1002/1521-4141(200106)31:6<1656::aid-immu1656>3.0.co;2-v.
Interleukin-2 (IL-2)-activated polyclonal or clonal NK cells lysed autologous antigen presenting cells (APC) through the engagement of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. NK cell-mediated cytolysis of APC correlated with the surface density of these NCR. Indeed, NK cell clones bearing low amounts of NKp30 and NKp46 did not lyse autologous APC, whereas NK cell clones with bright expression of these NCR efficiently killed autologous APC. Upon masking of NKp30 or NKp46 by specific monoclonal antibodies a strong reduction (by 50%) of APC lysis could be detected and the complete inhibition was achieved by the simultaneous masking of these NCR. Interestingly, NK cell-mediated APC lysis was impaired by the phosphatidylinositol 3-kinase (PI-3 K) inhibitors LY294002 or wortmannin. Similarly, these drugs strongly reduced NK cell activation triggered by NKp30 or NKp46 in a re-directed killing assay as well as the activation of Akt/PKB, substrate of PI-3 K, induced by the engagement of these receptors. Altogether, these findings strongly suggest that NCR are responsible for the killing of autologous APC through the activation of PI-3 K.
白细胞介素-2（IL-2）激活的多克隆或克隆性自然杀伤（NK）细胞通过自然细胞毒性受体（NCR）NKp30和NKp46的作用裂解自体抗原呈递细胞（APC）。NK细胞介导的APC细胞溶解作用与这些NCR的表面密度相关。实际上，携带少量NKp30和NKp46的NK细胞克隆不会裂解自体APC，而这些NCR高表达的NK细胞克隆则能有效杀伤自体APC。用特异性单克隆抗体封闭NKp30或NKp46后，可检测到APC裂解作用大幅降低（降低50%），同时封闭这些NCR则可实现完全抑制。有趣的是，磷脂酰肌醇3激酶（PI-3 K）抑制剂LY294002或渥曼青霉素会损害NK细胞介导的APC裂解作用。同样，在重定向杀伤试验中，这些药物也强烈降低了由NKp30或NKp46触发的NK细胞激活，以及这些受体作用诱导的PI-3 K底物Akt/PKB的激活。总之，这些发现强烈表明NCR通过激活PI-3 K负责杀伤自体APC。
