Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
J Immunol. 2013 Sep 15;191(6):2865-9. doi: 10.4049/jimmunol.1301500. Epub 2013 Aug 19.
NK cells are critical in immune responses against pathogens. However, their role in autoimmunity is still controversial. In this study, we demonstrate that neonatal NK cells render newborns more susceptible to neonatal autoimmunity induced by maternal autoantibodies (neonatal autoimmune ovarian disease); thus, neonatal but not adult NK cells are pathogenic after transfer into NK cell-deficient pups. The inhibitory receptors Ly49C/I are expressed in ∼5% of neonatal and ∼50% of adult NK cells. In this study, we show that the presence of Ly49C/I⁺ adult NK cells inhibits neonatal autoimmune ovarian disease induction. Thus, the ontogenetic regulation of Ly49C/I expression determines the propensity to autoantibody-induced autoimmunity. In summary, this study provides definitive evidence of a pathogenic role of NK cells in neonatal autoimmunity and also elucidates a novel mechanism by which neonatal NK cells render newborns more susceptible to autoantibody-induced autoimmunity.
自然杀伤 (NK) 细胞在针对病原体的免疫反应中起着至关重要的作用。然而，它们在自身免疫中的作用仍存在争议。在这项研究中，我们证明了新生儿 NK 细胞使新生儿更容易受到母体自身抗体引起的新生儿自身免疫的影响（新生儿自身免疫性卵巢疾病）；因此，新生而非成年 NK 细胞在转移到 NK 细胞缺陷幼崽后具有致病性。抑制性受体 Ly49C/I 在约 5%的新生儿和约 50%的成年 NK 细胞中表达。在这项研究中，我们表明 Ly49C/I⁺成年 NK 细胞的存在抑制了新生儿自身免疫性卵巢疾病的诱导。因此，Ly49C/I 表达的个体发育调节决定了自身抗体诱导自身免疫的倾向。总之，这项研究提供了 NK 细胞在新生儿自身免疫中具有致病性作用的明确证据，也阐明了一种新的机制，即新生儿 NK 细胞使新生儿更容易受到自身抗体诱导的自身免疫的影响。
