Vaccine Discovery Division, La Jolla Institute for Immunology, La Jolla, CA.
Faculty of Medicine, General Sir John Kotelawala Defense University, Ratmalana, Sri Lanka.
J Immunol. 2021 Jul 15;207(2):523-533. doi: 10.4049/jimmunol.2100011. Epub 2021 Jun 30.
Upon Ag encounter, T cells can rapidly divide and form an effector population, which plays an important role in fighting acute infections. In humans, little is known about the molecular markers that distinguish such effector cells from other T cell populations. To address this, we investigated the molecular profile of T cells present in individuals with active tuberculosis (ATB), where we expect Ag encounter and expansion of effector cells to occur at higher frequency in contrast to -sensitized healthy IGRA individuals. We found that the frequency of HLA-DR cells was increased in circulating CD4 T cells of ATB patients, and was dominantly expressed in Ag-specific CD4 T cells. We tested and confirmed that HLA-DR is a marker of recently divided CD4 T cells upon Ag exposure using an in vitro model examining the response of resting memory T cells from healthy IGRA to Ags. Thus, HLA-DR marks a CD4 T cell population that can be directly detected ex vivo in human peripheral blood, whose frequency is increased during ATB disease and contains recently divided Ag-specific effector T cells. These findings will facilitate the monitoring and study of disease-specific effector T cell responses in the context of ATB and other infections.
当遇到抗原时，T 细胞可以迅速分裂并形成效应细胞群体，这在对抗急性感染中起着重要作用。在人类中，对于区分这种效应细胞与其他 T 细胞群体的分子标记知之甚少。为了解决这个问题，我们研究了活跃性肺结核（ATB）个体中存在的 T 细胞的分子特征，我们预计在这些个体中，抗原接触和效应细胞的扩增会更频繁地发生，与致敏的健康 IGRA 个体相比。我们发现，循环 CD4 T 细胞中 HLA-DR 细胞的频率在 ATB 患者中增加，并且主要在 Ag 特异性 CD4 T 细胞中表达。我们使用体外模型检测了健康 IGRA 个体的静止记忆 T 细胞对 Ag 的反应，测试并证实 HLA-DR 是 Ag 暴露后新近分裂的 CD4 T 细胞的标志物。因此，HLA-DR 标记了一个可以在人类外周血中直接检测到的 CD4 T 细胞群体，其在 ATB 疾病期间增加，并包含最近分裂的 Ag 特异性效应 T 细胞。这些发现将有助于监测和研究 ATB 及其他感染情况下的疾病特异性效应 T 细胞反应。
