摘要
目的:探讨慢性乙型肝炎(CHB)患者外周血乙型肝炎病毒(HBV)特异性细胞毒性T淋巴细胞(CTLs)表面CD244与程序性死亡蛋白1(PD-1)的共表达模式及其与疾病进展的关系。方法:采集81例CHB患者和14例健康者外周血,分离外周血单个核细胞(PBMC);利用主要组织相容性复合体I(MHC-I)-肽五聚体技术标定HBV表位特异性CTLs;荧光抗体标记细胞表面CD244与PD-1分子,流式细胞术检测。结果:CHB患者CD244与PD-1在HBV特异性CTLs表面共表达较总CD8+T细胞表面明显升高(67.48%±17.16%vs 14.01%±7.97%,P<0.01);HBV感染的不同临床类型中,轻中度的CHB患者HBV特异性CTLs表面CD244与PD-1共表达水平较免疫耐受者明显升高(72.05%±16.86%vs 53.11%±18.05%,P<0.05),肝衰竭组CD244与PD-1共表达水平较轻中度CHB下调(63.11%±13.87%vs 72.05%±16.86%,P<0.05)并伴随干扰素γ(IFN-γ)分泌功能的恢复(30.95%±20.29%vs 13.63%±10.46%,P<0.01)。结论:CHB患者HBV特异性CTLs细胞表面高共表达CD244与PD-1分子,CD244与PD-1共表达在CHB不同临床类型中有差异,并与IFN-γ分泌水平呈负相关,提示CD244可能与CHB患者HBV特异性CTLs功能低下及CHB疾病进展相关。
AIM ： To investigate the co - expression of cluster of differentiation 244 （CD244） and programmed death 1 protein （ PD - 1 ） on hepatitis B virus （HBV） antigen - specific cytotoxic T - lymphocytes （CTLs） in chronic hep- atitis B （CHB） patients and its correlation with the clinical stages of HBV chronic infection. METHODS： Eighty- one CHB subjects with human leukocyte antigen - A2 （ HLA - A2） positive, including 20 cases of acute - on - chronic liver failure （ACLF）, 20 cases Of severe chronic hepatitis B （s -CHB）, 34 cases of mild and moderate chronic hepatitis B （m - CHB） and 7 cases of immune tolerant stage （IT） of chronic hepatitis B as well as 14 healthy controls （ HC）, were en- rolled in this study. The co - expression of CD244 and PD - 1 was analyzed in virus - specific CD8＋ T - cells derived from peripheral blood using major histocompatibility complex class Ⅰ （ MHC - Ⅰ） pentamers targeting immunodominant epitopes of HBV core antigen （18 -27）. RESULTS： In the patients with chronic HBV infection, virus -specific CD8＋T- cells with co - expression of CD244 and PD - 1 were at increased levels than those in total CD8＋T - cells （67.48%±17.16% vs 14.01% ±7.97%, P 〈0. 01 ） in the peripheral blood. Among different clinical stages, increased level of CD244 expres- sion coincided with increased expression of PD - 1 in m - CHB compared with IT of CHB （73.08%±8.63% vs 53.11%±18.05% , P 〈0. 05）, which was followed by decreased co - expression level in ACLF （63.11%±13.87% vs 72. 05%±16. 86%, P 〈0. 05） and restoration of the ability to secrete IFN - γ （30. 95%±20. 29% vs 13.63%±10. 46%, P 〈0. 05）. CONCLUSION： CD244 and PD- 1 are highly co- expressed in HBV- specific CTLs in the patients with s - CHB and m - CHB, and are decreased in ACLF following the restoration of IFN - γ secretion. The severity of CHB may be correlated with CD244 and PD -1 co- expression in HBV- specific CTLs.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2012年第12期2254-2260,共7页
Chinese Journal of Pathophysiology
基金
广东省自然科学基金资助项目(No.10151008901000059)
广东省计划项目(No.2009B030801127)
教育部留学回国人员基金资助项目(No.2010-1174)
