Adekambi Toidi, Ibegbu Chris C, Cagle Stephanie, Ray Susan M, Rengarajan Jyothi
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, United States.
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States.
Front Immunol. 2018 Jun 25;9:1481. doi: 10.3389/fimmu.2018.01481. eCollection 2018.
Antigen-specific CD4 T cell responses to (Mtb) infection are important for host defense against tuberculosis (TB). However, Mtb-specific IFN-γ-producing T cells do not distinguish active tuberculosis (ATB) patients from individuals with asymptomatic latent Mtb infection (LTBI). We reasoned that the immune phenotype of Mtb-specific IFN-γCD4 T cells could provide an indirect gauge of Mtb antigen load within individuals. We sought to identify immune markers in Mtb-specific IFN-γCD4 T cells and hypothesized that expression of caspase-3 Mtb-specific CD4 T cells would be associated with ATB. Using polychromatic flow cytometry, we evaluated the expression of caspase-3 in Mtb-specific CD4 T cells from LTBI and ATB as well as from ATB patients undergoing anti-TB treatment. We found significantly higher frequencies of Mtb-specific caspase-3IFN-γCD4 T cells in ATB compared to LTBI. Caspase-3IFN-γCD4 T cells were also more activated compared to their caspase-3-negative counterparts. Furthermore, the frequencies of caspase-3IFN-γCD4 T cells decreased in response to anti-TB treatment. Our studies suggest that the frequencies of caspase-3-expressing antigen-specific CD4 T cells may reflect mycobacterial burden and may be useful for distinguishing Mtb infection status along with other host biomarkers.
针对结核分枝杆菌（Mtb）感染的抗原特异性CD4 T细胞反应对于宿主抵御结核病（TB）至关重要。然而，结核分枝杆菌特异性产生干扰素-γ的T细胞无法区分活动性结核病（ATB）患者与无症状潜伏性结核分枝杆菌感染（LTBI）个体。我们推测，结核分枝杆菌特异性干扰素-γ CD4 T细胞的免疫表型可以间接衡量个体内结核分枝杆菌抗原负荷。我们试图鉴定结核分枝杆菌特异性干扰素-γ CD4 T细胞中的免疫标志物，并假设半胱天冬酶-3在结核分枝杆菌特异性CD4 T细胞中的表达与活动性结核病相关。我们使用多色流式细胞术评估了来自潜伏性结核感染和活动性结核病以及接受抗结核治疗的活动性结核病患者的结核分枝杆菌特异性CD4 T细胞中半胱天冬酶-3的表达。我们发现，与潜伏性结核感染相比，活动性结核病中结核分枝杆菌特异性半胱天冬酶-3+干扰素-γ+ CD4 T细胞的频率显著更高。与半胱天冬酶-3阴性的对应细胞相比，半胱天冬酶-3+干扰素-γ+ CD4 T细胞也更活化。此外，抗结核治疗后，半胱天冬酶-3+干扰素-γ+ CD4 T细胞的频率下降。我们的研究表明，表达半胱天冬酶-3的抗原特异性CD4 T细胞的频率可能反映分枝杆菌负荷，并且可能有助于与其他宿主生物标志物一起区分结核分枝杆菌感染状态。
