Vankayalapati Ramakrishna, Wizel Benjamin, Weis Stephen E, Safi Hassan, Lakey David L, Mandelboim Ofer, Samten Buka, Porgador Angel, Barnes Peter F
Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler, TX 75708, USA.
J Immunol. 2002 Apr 1;168(7):3451-7. doi: 10.4049/jimmunol.168.7.3451.
We used human tuberculosis as a model to investigate the role of NK cytotoxic mechanisms in the immune response to intracellular infection. Freshly isolated NK cells and NK cell lines from healthy donors lysed Mycobacterium tuberculosis-infected monocytes to a greater extent than uninfected monocytes. Lysis of infected monocytes was associated with increased expression of mRNA for the NKp46 receptor, but not the NKp44 receptor. Antisera to NKp46 markedly inhibited lysis of infected monocytes. NK cell-mediated lysis was not due to reduced expression of MHC class I molecules on the surface of infected monocytes or to enhanced production of IL-18 or IFN-gamma. NK cell lytic activity against M. tuberculosis-infected monocytes and NKp46 mRNA expression were reduced in tuberculosis patients with ineffective immunity to M. tuberculosis compared with findings in healthy donors. These observations suggest that 1) the NKp46 receptor participates in NK cell-mediated lysis of cells infected with an intracellular pathogen, and 2) the reduced functional capacity of NK cells is associated with severe manifestations of infectious disease.
我们以人类结核病为模型，研究自然杀伤细胞（NK）细胞毒性机制在细胞内感染免疫反应中的作用。从健康供体新鲜分离的NK细胞和NK细胞系对结核分枝杆菌感染的单核细胞的裂解程度比未感染的单核细胞更高。感染单核细胞的裂解与NKp46受体而非NKp44受体的mRNA表达增加有关。抗NKp46抗血清显著抑制感染单核细胞的裂解。NK细胞介导的裂解并非由于感染单核细胞表面MHC I类分子表达降低，也不是由于IL-18或IFN-γ产生增加。与健康供体相比，对结核分枝杆菌免疫无效的结核病患者中，NK细胞对结核分枝杆菌感染单核细胞的裂解活性和NKp46 mRNA表达降低。这些观察结果表明：1）NKp46受体参与NK细胞介导的对细胞内病原体感染细胞的裂解；2）NK细胞功能能力降低与传染病的严重表现相关。
