Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India.
Front Immunol. 2019 Jul 12;10:1521. doi: 10.3389/fimmu.2019.01521. eCollection 2019.
We investigated the influence of a transient treatment of corticosteroid on CD8 T cells during herpesvirus infection. Dexamethasone, a synthetic corticosteroid, induced apoptosis of naïve and memory CD8 T cells but virus-specific effector cells were spared. CD8 T cell susceptibility was directly correlated with the expression of nr3c1. Both α-(HSV1) and γ-(MHV68) herpesvirus infection expanded CD8 T cells down regulated nr3c1 indicating corticosteroid-mediated effects were not limited to one pathogen or the specific clonotype. Dexamethasone compromised anti-viral immunity to subsequent infections, likely through reductions in the naïve cell pool. Dexamethasone augmented the function and inflammatory tissue homing potential of effector cells via upregulation of CXCR3. Accordingly, an antibody neutralization of CXCR3 diminished dexamethasone-induced migration of CD8 T cells to tissues resulting in increased virus burden. Our study therefore suggests that even a transient corticosteroid therapy influences both ongoing CD8 T cell responses as well as the size of the naïve and memory repertoire.
我们研究了在疱疹病毒感染期间，皮质类固醇的短暂治疗对 CD8 T 细胞的影响。地塞米松是一种合成的皮质类固醇，它诱导幼稚和记忆 CD8 T 细胞凋亡，但病毒特异性效应细胞不受影响。CD8 T 细胞的易感性与 nr3c1 的表达直接相关。α-（HSV1）和γ-（MHV68）疱疹病毒感染都使 CD8 T 细胞数量减少，nr3c1 下调，表明皮质类固醇介导的作用不仅限于一种病原体或特定的克隆型。地塞米松削弱了对随后感染的抗病毒免疫力，可能是通过减少幼稚细胞池。地塞米松通过上调 CXCR3 增强效应细胞的功能和炎症组织归巢潜能。因此，一种 CXCR3 的抗体中和减少了地塞米松诱导的 CD8 T 细胞向组织的迁移，导致病毒载量增加。因此，我们的研究表明，即使是短暂的皮质类固醇治疗也会影响正在进行的 CD8 T 细胞反应以及幼稚和记忆库的大小。
