CAJ | 학술논문

目的观察急性自限性乙型肝炎发病过程中患者体内病毒抗原特异性细胞毒性T淋巴细胞(CTL)上程序性细胞死亡受体1(PD-1)表达的动态变化特点及其与记忆性抗原特异性CD8+T淋巴细胞形成的关系. 方法针对不同表位合成4种五聚体,长期随访收集11例人类白细胞抗原(HLA)-A2阳性的急性乙型肝炎患者的外周血,流式细胞仪检测病毒特异性CTL上免疫抑制性分子PD-1、记忆性分子(CCR7、CD45RA、CD127)和活化标志物CD38的表达情况,并分析其相关性.同时进行肝功能,HBsAg、抗-HBs和血清HBV DNA载量检测.结果所有急性自限性乙型肝炎患者发病早期均表现出高频度、病毒抗原多表位的特异性CTL反应,而晚期各表位CTL频率均明显下降.CTL上PD-1表达在早期明显上调;与早期比较,晚期PD-1分子的表达明显降低(t=4.314,P＜0.01).同时CTL高表达记忆性分子CCR7,CD45RA和CD127,而低表达活化标志物CD38.提示病毒清除后记忆性CD8+T淋巴细胞形成. 结论在急性自限性乙型肝炎发病过程中,HBV特异性CTL上PD-1分子表达的动态变化与记忆性T淋巴细胞的形成密切相关.
목적 관찰급성자한성을형간염발병과정중환자체내병독항원특이성세포독성T림파세포(CTL)상정서성세포사망수체1(PD-1)표체적동태변화특점급기여기억성항원특이성CD8+T림파세포형성적관계. 방법 침대불동표위합성4충오취체,장기수방수집11례인류백세포항원(HLA)-A2양성적급성을형간염환자적외주혈,류식세포의검측병독특이성CTL상면역억제성분자PD-1、기억성분자(CCR7、CD45RA、CD127)화활화표지물CD38적표체정황,병분석기상관성.동시진행간공능,HBsAg、항-HBs화혈청HBV DNA재량검측.결과소유급성자한성을형간염환자발병조기균표현출고빈도、병독항원다표위적특이성CTL반응,이만기각표위CTL빈솔균명현하강.CTL상PD-1표체재조기명현상조;여조기비교,만기PD-1분자적표체명현강저(t=4.314,P＜0.01).동시CTL고표체기억성분자CCR7,CD45RA화CD127,이저표체활화표지물CD38.제시병독청제후기억성CD8+T림파세포형성. 결론 재급성자한성을형간염발병과정중,HBV특이성CTL상PD-1분자표체적동태변화여기억성T림파세포적형성밀절상관.
Objectives Programmed death-1 (PD-1) up-regulation impairs virns-specific CD8+ Tcell responses during chronic viral infection. Whether PD-1 expression influences the virus-specific CD8+ T cells in humans with acute viral infection reinains largely undefined. This study aims to characterize the PD-1 expression during acute hepatitis B (AHB), and further addresses the association between the PD-1 dynamics and memory T-cell formation during acute HBV infection. Methods Peripheral HBV-specific CD8+ T cells from 11 HLA-A2-positive AHB patients were longitudinally quantitatively analyzed, and PD-1, memory markers CCR7, CD45RA and CD127 and activation marker CD38 on HBV-specific CD8+ T cells were measured using flow cytometric assay. Serum ALT, HBsAg, HBsAb and HBV-DNA levels were evaluated for each subject. Results All 11 AHB patients examined had multiple pentamer-positive CD8+ T-cell responses in their early phase of HBV infection. Specifically, their PD-1 on pentamer-positive CD8+ T-ceils was significantly up-regulated at the onset of their disease. Following their disease resolution, the dynamic decrease in PD- 1 expression was found to correlate with the phenotypic development of memory CD8+ T cells, indicated by the increases in CCR7, CEM5RA and CD127 and decrease in CD38. Conclusion PD-1-mediated negative signaling may be closely associated with memory T-cell formation during acute self-limited hepatitis B.