人类免疫缺陷病毒阴性隐球菌性脑膜炎患者外周血淋巴细胞亚群分析

摘要

目的 分析人类免疫缺陷病毒(Human immunodeficiency virus,HIV)阴性隐球菌性脑膜炎(Cryptococcal meningitis,CM)患者外周血淋巴细胞亚群改变特点,深化对隐球菌病发病机制的认识.方法 筛选HIV阴性CM患者31例和健康献血员21例进行淋巴细胞亚群分析,CM患者根据是否存在免疫抑制基础疾病分为两个亚组,比较3组研究对象淋巴细胞亚群中B、NK、CD4+T、CD8+T细胞亚群,CD4+T及CD8+T细胞的第二信号受体CD28表达比例及CD8+T细胞激活标记物HLA-DR、CD38的表达水平.结果 有基础病CM组B、NK、CD4+T和CD8+T 4种亚群中位数依次为56×106/L、86×106/L、218×106/L、164×106/L,显著低于健康对照组的223×106/L、280×106/L、695×106/L、521×106/L(P值均＜0.001),同时存在CD8+T细胞激活亚群比例较健康对照显著升高.无基础病CM患者上述4种细胞亚群中位数依次为128×106/L、128×106/L、567×106/L、527×106/L,除CD8+T细胞计数水平与健康对照相似以外,B(P =0.02)、NK (P=0.002)和CD4+T细胞(P=0.03)计数均低于健康对照,其CD8+T细胞激活亚群比例与健康对照组相似.CD4+T和CD8+T细胞的CD28表达水平在3组间未见显著差异.结论 HIV阴性CM患者,无论是否存在免疫抑制基础疾病,外周血B、NK及CD4+T 3种细胞计数可出现同时减少.%Objective To find if immunophenotypic features of peripheral lymphocytes was associated with risk of cryptococcal meningitis (CM) in HIV-negative individuals.Methods A total of 31 CM patients treated at a tertiary hospital in Beijing,China were included.They were divided into immunocompromised comorbidity group (n =16) and apparently immunocompetent group (n =15).Twenty-one healthy donors were included as control group.Lymphocyte subsets including B,NK,CD4 +T,and CD8+ T cells,CD28 expression on T cells,and activation markers (HLA-DR and CD38) on CD8+ T cells were determined by flow cytometry and compared among the three groups.Results Compared with healthy donors,immunocompromised comorbidity group had dramatically decreased median B cell (223 vs.56/μL),NK cell (280 vs.86/μL),CD4+ T cell (695 vs.218/μL),and CD8+T cell (521 vs.164/μL) counts (P values for all four subsets＜0.001).Proportions of activated CD8+ T cells were significantly increased in immunocompromised patients than that in healthy control.Except for CD8+ T cell counts (527/μL),the median B cell (128/μL,P=0.02),NK cell (128/μL,P=0.002) and CD4+ T cell (567/μL,P =0.03)were moderately reduced in the apparently immunocompetent group than those in the healthy donors.The levels of HLA-DR and CD38 on CD8+ T cells in the apparently immunocompetent group were similar with the healthy donors.CD28 expression on CD4+ T and CD8+ T cells did not differ among the three groups.Conclusions The immunophenotype of CM patients with immunocompromised comorbidity was characterized by generalized decreased B,NK,CD4+ T,and CD8+ T cells.Mild-to-moderate reduce in B cell,NK cell and CD4+ T cell counts were observed in apparently immunocompetent patients.