抗逆转录病毒和抗结核治疗对合并感染患者 CD4 和 CD8 HIV/M. tuberculosis 特异性 T 细胞的影响。
Impact of antiretroviral and tuberculosis therapies on CD4 and CD8 HIV/M. tuberculosis-specific T-cell in co-infected subjects.
机构信息
Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy.
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico P. Giaccone, Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
出版信息
Immunol Lett. 2018 Jun;198:33-43. doi: 10.1016/j.imlet.2018.04.001. Epub 2018 Apr 7.
BACKGROUND
Human Immunodeficiency Virus (HIV) infection is a risk factor for tuberculosis (TB). Antiretroviral therapy (ART) changed HIV clinical management but it is still unclear how pre-existing HIV/Mycobacterium tuberculosis (Mtb)-specific CD4 and CD8 T-cells are restored.
AIM
to evaluate the impact of ART and TB therapies on the functional and phenotypic profile of Mtb-specific antigen-response of CD4 and CD8 T-cells in prospectively enrolled HIV-TB co-infected patients.
METHODS
ART-naïve HIV-infected patients, with or without active TB or latent TB infection (LTBI), were enrolled before and after starting ART and TB therapies. Peripheral blood mononuclear cells (PBMC) were stimulated overnight with Mtb and HIV antigens (GAG). Cytokine expression and phenotype profile were evaluated by flow cytometry. Cytomegalovirus (CMV) and staphylococcal enterotoxin B (SEB) were also used.
RESULTS
The median of absolute number of CD4 T-cells increased after ART and TB therapies in all groups analyzed, while the median of absolute number of CD8 T-cells decreases in HIV and HIV-LTBI groups. Treatments significantly increased the frequency of Mtb-specific CD4 T-cells in the HIV-LTBI (p = 0.015) with a rise of the central memory compartment. The magnitude of the CD4 T-cell response to HIV-GAG significantly increased in active TB (p = 0.03), whereas the magnitude of CMV-specific CD4 T-cell response decreased in all the groups. Similarly, the treatments increased the number of Mtb-specific CD8 responders in both HIV-LTBI and HIV-TB groups, whereas the phenotype distribution was dependent on the antigens used and on the stage of infection/disease.
CONCLUSIONS
After therapies the median of absolute number and the proportion of CD4 T-cells increased in all groups whereas the median of absolute count and proportion of CD8 T-cells decreased in the HIV and HIV-LTBI subjects. Interestingly, an increased frequency of CD4 T-cell response to RD1 proteins in HIV-LTBI subjects was found. These results contribute to a better understanding of the effect of ART and TB therapies on the modulation of Mtb-specific CD4 and CD8 T-cells subsets.
背景
人类免疫缺陷病毒（HIV）感染是结核病（TB）的一个风险因素。抗逆转录病毒疗法（ART）改变了 HIV 的临床管理，但 HIV/结核分枝杆菌（Mtb）特异性 CD4 和 CD8 T 细胞如何恢复仍不清楚。
目的
评估 ART 和 TB 疗法对前瞻性纳入的 HIV-TB 合并感染患者 Mtb 特异性抗原反应的 CD4 和 CD8 T 细胞的功能和表型特征的影响。
方法
在开始 ART 和 TB 治疗之前和之后，纳入了未经 ART 治疗的 HIV 感染患者，无论是否有活动性 TB 或潜伏性 TB 感染（LTBI）。用 Mtb 和 HIV 抗原（GAG）刺激外周血单核细胞（PBMC）过夜。通过流式细胞术评估细胞因子表达和表型特征。还使用了巨细胞病毒（CMV）和葡萄球菌肠毒素 B（SEB）。
结果
在所有分析的组中，ART 和 TB 治疗后 CD4 T 细胞的绝对数中位数增加，而 HIV 和 HIV-LTBI 组的 CD8 T 细胞的绝对数中位数减少。治疗显著增加了 HIV-LTBI 组中 Mtb 特异性 CD4 T 细胞的频率（p=0.015），并增加了中央记忆细胞的数量。在活动性 TB 中，HIV-GAG 特异性 CD4 T 细胞反应的幅度显著增加（p=0.03），而所有组的 CMV 特异性 CD4 T 细胞反应幅度下降。同样，治疗增加了 HIV-LTBI 和 HIV-TB 组中 Mtb 特异性 CD8 反应者的数量，而表型分布取决于所使用的抗原和感染/疾病的阶段。
结论
治疗后，所有组的 CD4 T 细胞的绝对数中位数和比例均增加，而 HIV 和 HIV-LTBI 组的 CD8 T 细胞的绝对数中位数和比例均减少。有趣的是，在 HIV-LTBI 患者中发现了对 RD1 蛋白的 CD4 T 细胞反应频率增加。这些结果有助于更好地了解 ART 和 TB 疗法对 Mtb 特异性 CD4 和 CD8 T 细胞亚群的调节作用。
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