Morishima Satoko, Nakamura Shigeo, Yamamoto Kazuhito, Miyauchi Hidemasa, Kagami Yoshitoyo, Kinoshita Tomohiro, Onoda Hiroshi, Yatabe Yasushi, Ito Masafumi, Miyamura Kouichi, Nagai Hirokazu, Moritani Suzuko, Sugiura Isamu, Tsushita Keitaro, Mihara Hidetsugu, Ohbayashi Kaneyuki, Iba Sachiko, Emi Nobuhiko, Okamoto Masataka, Iwata Seiko, Kimura Hiroshi, Kuzushima Kiyotaka, Morishima Yasuo
Department of Hematology, Fujita Health University School of Medicine , Toyoake , Japan.
Leuk Lymphoma. 2015 Apr;56(4):1072-8. doi: 10.3109/10428194.2014.938326. Epub 2014 Aug 13.
The immunological status of patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) without obvious immunodeficiency has not been elucidated. A multicenter prospective study was conducted to assess pretreatment T-cell responses to EBV, EBV-DNA load and anti-EBV antibody in these patients. The proliferative and interferon (IFN)-γ-producing capacity of T-cells in response to autologous B-lymphoblastoid cell lines was determined using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay. Frequencies of EBV-specific CD4+ T-cells in patients with EBV+ DLBCL (n = 13) were significantly higher than in healthy controls (HCs) (n = 16) after both ex vivo and in vitro stimulation. Frequencies of EBV-specific CD8+ T-cells in patients with EBV+ DLBCL tended to be higher than in HCs after in vitro stimulation. Patients with EBV+ DLBCL also showed increased immunoglobulin G (IgG) responses to lytic EBV-encoded antigens. Pretreatment plasma EBV-DNA level was significantly higher in patients with EBV+ DLBCL than in patients with EBV- DLBCL or HCs. In conclusion, EBV-specific T-cells showed increased reactivity, accompanied by higher levels of plasma virus DNA in patients with EBV+ DLBCL.
在没有明显免疫缺陷的爱泼斯坦-巴尔病毒阳性弥漫性大B细胞淋巴瘤(EBV+ DLBCL)患者中,其免疫状态尚未阐明。我们开展了一项多中心前瞻性研究,以评估这些患者预处理时T细胞对EBV的反应、EBV-DNA载量及抗EBV抗体情况。使用基于羧基荧光素二乙酸琥珀酰亚胺酯(CFSE)的检测方法,测定T细胞对自体B淋巴母细胞系反应时的增殖能力及产生干扰素(IFN)-γ的能力。体外和体内刺激后,EBV+ DLBCL患者(n = 13)中EBV特异性CD4+ T细胞的频率显著高于健康对照(HCs)(n = 16)。体外刺激后,EBV+ DLBCL患者中EBV特异性CD8+ T细胞的频率往往高于HCs。EBV+ DLBCL患者对裂解型EBV编码抗原的免疫球蛋白G(IgG)反应也有所增强。EBV+ DLBCL患者预处理时血浆EBV-DNA水平显著高于EBV- DLBCL患者或HCs。总之,EBV特异性T细胞反应性增强,同时EBV+ DLBCL患者血浆病毒DNA水平更高。