Voogd Linda, Riou Catherine, Scriba Thomas J, van Wolfswinkel Marjolein, van Meijgaarden Krista E, Franken Kees L M C, Wilkinson Robert J, Ottenhoff Tom H M, Joosten Simone A
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Front Immunol. 2024 Dec 23;15:1505329. doi: 10.3389/fimmu.2024.1505329. eCollection 2024.
Tuberculosis (TB) is the deadliest infectious disease worldwide and novel vaccines are urgently needed. HLA-E is a virtually monomorphic antigen presentation molecule and is not downregulated upon HIV co-infection. HLA-E restricted specific CD8 T cells are present in the circulation of individuals with active TB (aTB) and infection (TBI) with or without HIV co-infection, making HLA-E restricted T cells interesting vaccination targets for TB.
Here, we performed in-depth phenotyping of HLA-E/ specific and total T cell populations in individuals with TBI and in individuals with aTB or TBI and HIV using HLA-E/ tetramers.
We show that HIV co-infection is the main driver in changing the memory distribution of HLA-E/ specific CD4 and CD8 T cell subsets. HLA-E/ specific CD4 and CD8 T cells were found to circulate with comparable frequencies in all individuals and displayed expression of KLRG1, PD-1 and 2B4 similar to that of total T cells. The presence of HLA-E/ specific T cells in individuals with aTB and TBI highlights the potential of HLA-E as a vaccine target for TB.
结核病(TB)是全球最致命的传染病,迫切需要新型疫苗。HLA-E是一种几乎单态的抗原呈递分子,在合并感染HIV时不会下调。HLA-E限制性特异性CD8 T细胞存在于活动性结核病(aTB)患者以及合并或未合并HIV感染的潜伏性结核感染(TBI)患者的循环中,这使得HLA-E限制性T细胞成为结核病疫苗的有趣靶点。
在此,我们使用HLA-E/四聚体对TBI患者以及aTB或TBI合并HIV感染的患者中的HLA-E/特异性和总T细胞群体进行了深入表型分析。
我们表明,HIV合并感染是改变HLA-E/特异性CD4和CD8 T细胞亚群记忆分布的主要驱动因素。发现HLA-E/特异性CD4和CD8 T细胞在所有个体中的循环频率相当,并且与总T细胞类似,表达KLRG1、PD-1和2B4。aTB和TBI患者中存在HLA-E/特异性T细胞,这突出了HLA-E作为结核病疫苗靶点的潜力。