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