多发性硬化症患者对感染 Epstein-Barr 病毒的 B 细胞的 CD8+ T 细胞反应降低，并不是由于 B 细胞或单核细胞上 HLA Ⅰ类分子表达降低所致。
Decreased CD8+ T cell response to Epstein-Barr virus infected B cells in multiple sclerosis is not due to decreased HLA class I expression on B cells or monocytes.
机构信息
The University of Queensland, School of Medicine, Health Sciences Building, Royal Brisbane and Women's Hospital, Queensland 4029, Australia.
出版信息
BMC Neurol. 2011 Aug 3;11:95. doi: 10.1186/1471-2377-11-95.
BACKGROUND
Patients with multiple sclerosis (MS) have a decreased frequency of CD8+ T cells reactive to their own Epstein-Barr virus (EBV) infected B cells. We have proposed that this might predispose to the development of MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. The decreased CD8+ T cell response to EBV results from a general CD8+ T cell deficiency and also a decreased proportion of EBV-specific T cells within the total CD8+ T cell population. Because decreased HLA class I expression on monocytes and B cells has been reported in MS and could influence the generation and effector function of EBV-specific CD8+ T cells, the present study was undertaken to measure the expression of HLA molecules on B cells and monocytes in patients with MS.
METHODS
We used flow cytometry to determine the proportions of T cells, natural killer cells, B cells and monocytes in peripheral blood mononuclear cells (PBMC) and to quantify the expression of HLA molecules on T cells, B cells and monocytes of 59 healthy subjects and 62 patients with MS who had not received corticosteroids or immunomodulatory therapy in the previous 3 months.
RESULTS
The levels of HLA class I and class II molecules expressed on T cells, B cells and monocytes were normal in patients with MS, with the exception of two patients with secondary progressive MS with very low class II expression on B cells. In confirmation of previous studies we also found that the percentage of CD8+ T cells was significantly decreased whereas the percentage of CD4+ T cells and the CD4:CD8 ratio were significantly increased in patients with MS compared to healthy subjects.
CONCLUSIONS
The decreased CD8+ T cell response to EBV-infected B cells in MS patients is not due to decreased HLA class I expression on monocytes or B cells. In a small proportion of patients decreased HLA class II expression on B cells might impair the CD8+ T cell response to EBV by reducing CD4+ T cell help.
背景
多发性硬化症（MS）患者对自身 EBV 感染的 B 细胞的 CD8+T 细胞反应频率降低。我们提出，这可能通过允许 EBV 感染的自身反应性 B 细胞在中枢神经系统中积累而导致 MS 的发生。对 EBV 的 CD8+T 细胞反应降低是由于 CD8+T 细胞普遍缺乏，以及在总 CD8+T 细胞群体中 EBV 特异性 T 细胞的比例降低。由于在 MS 中已经报道了单核细胞和 B 细胞上 HLA Ⅰ类分子表达降低，并且可能影响 EBV 特异性 CD8+T 细胞的产生和效应功能，因此进行了本研究以测量 MS 患者 B 细胞和单核细胞上 HLA 分子的表达。
方法
我们使用流式细胞术确定外周血单核细胞（PBMC）中 T 细胞、自然杀伤细胞、B 细胞和单核细胞的比例，并定量测量 59 名健康受试者和 62 名未接受皮质类固醇或免疫调节治疗的 MS 患者 PBMC 中 T 细胞、B 细胞和单核细胞上 HLA 分子的表达在过去 3 个月。
结果
除了两名患有继发性进行性 MS 的患者的 B 细胞上 II 类表达极低外，MS 患者的 T 细胞、B 细胞和单核细胞上的 HLA Ⅰ类和 II 类分子的表达水平正常。与之前的研究一致，我们还发现与健康受试者相比，MS 患者的 CD8+T 细胞百分比显著降低，而 CD4+T 细胞百分比和 CD4:CD8 比值显著增加。
结论
MS 患者对 EBV 感染的 B 细胞的 CD8+T 细胞反应降低不是由于单核细胞或 B 细胞上 HLA Ⅰ类分子表达降低所致。在一小部分患者中，B 细胞上 HLA Ⅱ类表达降低可能通过减少 CD4+T 细胞的帮助而损害对 EBV 的 CD8+T 细胞反应。
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