Jalbert Emilie, Liu Cuining, Mave Vidya, Lang Nancy, Kagal Anju, Valvi Chhaya, Paradkar Mandar, Gupte Nikhil, Lokhande Rahul, Bharadwaj Renu, Kulkarni Vandana, Gupta Amita, Weinberg Adriana
Department of Pediatrics, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, USA.
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, USA.
iScience. 2023 Jul 20;26(8):107425. doi: 10.1016/j.isci.2023.107425. eCollection 2023 Aug 18.
There is great need for vaccines against tuberculosis (TB) more efficacious than the licensed BCG. Our goal was to identify new vaccine benchmarks by identifying immune responses that distinguish individuals able to eradicate the infection (TB-resisters) from individuals with latent infection (LTBI-participants). TB-resisters had higher frequencies of circulating CD8 glucose monomycolate (GMM)+ Granzyme-B+ T cells than LTBI-participants and higher proportions of polyfunctional conventional and nonconventional T cells expressing Granzyme-B and/or PD-1 after stimulation of blood mononuclear cells. LTBI-participants had higher expression of activation markers and cytokines, including IL10, and IFNγ. An exploratory analysis of BCG-recipients with minimal exposure to TB showed absence of CD8+GMM+Granzyme-B+ T cells, lower or equal proportions of Granzyme-B+PD-1+ polyfunctional T cells than TB-resisters and higher or equal than LTBI-participants. In conclusion, high Granzyme-B+PD-1+ T cell responses to and, possibly, of CD8+GMM+Granzyme-B+ T cells may be desirable for new TB vaccines.
比起已获许可的卡介苗，人们迫切需要更有效的抗结核疫苗。我们的目标是通过识别能区分有能力根除感染的个体（结核抵抗者）和潜伏感染个体（LTBI参与者）的免疫反应，来确定新的疫苗基准。结核抵抗者循环中的CD8葡萄糖单霉菌酸酯（GMM）+颗粒酶B+T细胞频率高于LTBI参与者，在刺激血液单核细胞后，表达颗粒酶B和/或PD-1的多功能传统和非传统T细胞比例更高。LTBI参与者的激活标志物和细胞因子（包括IL10和IFNγ）表达更高。对极少接触结核的卡介苗接种者进行的探索性分析显示，不存在CD8+GMM+颗粒酶B+T细胞，颗粒酶B+PD-1+多功能T细胞比例低于或等于结核抵抗者，高于或等于LTBI参与者。总之，新的结核疫苗可能需要高颗粒酶B+PD-1+T细胞反应以及可能的CD8+GMM+颗粒酶B+T细胞反应。
