Fernandez Nadine C, Treiner Emmanuel, Vance Russell E, Jamieson Amanda M, Lemieux Suzanne, Raulet David H
Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Blood. 2005 Jun 1;105(11):4416-23. doi: 10.1182/blood-2004-08-3156. Epub 2005 Feb 22.
It is widely believed that self-tolerance of natural killer (NK) cells occurs because each NK cell expresses at least one inhibitory receptor specific for a host major histocompatibility complex (MHC) class I molecule. Here we report that some NK cells lack all known self-MHC-specific inhibitory receptors, yet are nevertheless self-tolerant. These NK cells exhibit a normal cell surface phenotype and some functional activity. However, they respond poorly to class I-deficient normal cells, tumor cells, or cross-linking of stimulatory receptors, suggesting that self-tolerance is established by dampening stimulatory signaling. Thus, self-tolerance of NK cells in normal animals can occur independently of MHC-mediated inhibition, and hyporesponsiveness plays a role in self-tolerance of NK cells, as also proposed for B and T cells.
人们普遍认为，自然杀伤（NK）细胞的自身耐受性之所以产生，是因为每个NK细胞至少表达一种针对宿主主要组织相容性复合体（MHC）I类分子的抑制性受体。在此我们报告，一些NK细胞缺乏所有已知的自身MHC特异性抑制性受体，但仍具有自身耐受性。这些NK细胞表现出正常的细胞表面表型和一些功能活性。然而，它们对I类缺陷的正常细胞、肿瘤细胞或刺激受体的交联反应较差，这表明自身耐受性是通过抑制刺激信号来建立的。因此，正常动物中NK细胞的自身耐受性可以独立于MHC介导的抑制而发生，并且反应低下在NK细胞的自身耐受性中起作用，正如对B细胞和T细胞所提出的那样。
