The Jackson Laboratory, Bar Harbor, ME 04609, USA.
J Immunol. 2011 Nov 1;187(9):4695-704. doi: 10.4049/jimmunol.1101776. Epub 2011 Sep 30.
Dysregulation of the T cell-dependent Ab response can lead to numerous immunological disorders, ranging from systemic lupus erythematosus to B cell lymphomas. Cellular processes governed by MHC class II proteins play a major role in this response and its dysregulation. The extent to which processes controlled by the diverse family of MHC class I proteins impact such autoimmune and neoplastic disorders, however, is less clear. In this study, we genetically dissect the contributions of individual MHC class I family members and the pathological processes under their control in the systemic lupus erythematosus-like disease of BXSB.Yaa mice and B cell lymphomagenesis of SJL mice. This study reveals a powerful repressive regulatory axis comprised of MHC class I-dependent CD8(+) T cells and NK cells. These results indicate that the predominant role of the MHC class I protein family in such immunological disorders is to protect from more aggressive diseases.
T 细胞依赖性 Ab 反应的失调可导致多种免疫性疾病，从系统性红斑狼疮到 B 细胞淋巴瘤不等。MHC II 类蛋白所调控的细胞过程在该反应及其失调中起着重要作用。然而，由 MHC I 类蛋白家族控制的各种过程对自身免疫和肿瘤性疾病的影响程度尚不清楚。在这项研究中，我们通过基因敲除的方法，在 BXSB.Yaa 小鼠的系统性红斑狼疮样疾病和 SJL 小鼠的 B 细胞淋巴瘤发生中，对单个 MHC I 类家族成员及其所调控的病理过程的作用进行了剖析。本研究揭示了一个由 MHC I 类依赖性 CD8(+)T 细胞和 NK 细胞组成的强大抑制性调控轴。这些结果表明，MHC I 类蛋白家族在这些免疫性疾病中的主要作用是防止更具侵袭性的疾病。
