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在潜伏性结核感染人群中,HIV合并感染与结核分枝杆菌特异性CD4 T细胞的HLA-DR表达增加有关。

HIV co-infection is associated with increased HLA-DR expression by Mycobacterium tuberculosis-specific CD4 T cells in people with latent tuberculosis infection.

作者信息

Khayumbi Jeremiah, Sasser Loren E, McLaughlin Taryn A, Ongalo Joshua, Tonui Joan, Ouma Samuel Gurrion, Campbell Angie, Odhiambo Felix Hayara, Gandhi Neel R, Kiprotich Chelimo, Day Cheryl L

机构信息

Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Biomedical Sciences, School of Public Health and Community Development, Maseno University, Kisumu, Kenya.

Emory Vaccine Center, Emory University, Atlanta, GA, USA; Emory National Primate Research Center, Atlanta, GA, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

Tuberculosis (Edinb). 2025 Mar;151:102607. doi: 10.1016/j.tube.2025.102607. Epub 2025 Jan 20.

Abstract

Infection with HIV is associated with dysregulated CD4 T cell responses to Mycobacterium tuberculosis (Mtb) and increased risk of developing tuberculosis. Mtb-specific CD4 T cells in people with HIV have diminished Th1 cytokine production capacity, thus we utilized a flow cytometry-based assay to measure CD40L expression by Mtb-specific CD4 T cells in a cytokine-independent manner. We evaluated the frequency and phenotype of Mtb-specific CD4 responses in Kenyan adults with latent Mtb infection and found that the majority of Mtb-specific CD4 T cells expressed CD40L in the absence of IFN-γ, regardless of HIV infection status. Expression of HLA-DR was increased on Mtb-specific CD4 T cells in people with HIV, compared to people without HIV. These data suggest expression of HLA-DR by Mtb-specific CD4 T cells may represent an early biomarker of increased mycobacterial antigen stimulation in people with HIV prior to the development of symptomatic tuberculosis disease.

摘要

感染人类免疫缺陷病毒(HIV)与CD4 T细胞对结核分枝杆菌(Mtb)的反应失调以及患结核病风险增加有关。HIV感染者中针对Mtb的CD4 T细胞产生Th1细胞因子的能力减弱,因此我们采用了一种基于流式细胞术的检测方法,以细胞因子非依赖的方式测量针对Mtb的CD4 T细胞上CD40L的表达。我们评估了肯尼亚潜伏性Mtb感染成年人群中针对Mtb的CD4反应的频率和表型,发现无论HIV感染状态如何,大多数针对Mtb的CD4 T细胞在缺乏干扰素-γ的情况下表达CD40L。与未感染HIV的人相比,HIV感染者中针对Mtb的CD4 T细胞上HLA-DR的表达增加。这些数据表明,在有症状的结核病发生之前,针对Mtb的CD4 T细胞上HLA-DR的表达可能代表HIV感染者中分枝杆菌抗原刺激增加的早期生物标志物。

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