Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy.

ABSTRACT: After Mycobacterium tuberculosis (Mtb) infection, many effector T cells traffic to the lungs, but few become activated. Here we use an antigen receptor reporter mouse (Nur77-GFP) to identify recently activated CD4 T cells in the lungs. These Nur77-GFP^HI cells contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFP^LO cells. By contrast, Nur77-GFP^LO cells express markers of terminal exhaustion and cytotoxicity, and the trafficking receptor S1pr5, associated with vascular localization. A short course of immunotherapy targeting OX40⁺ cells transiently expands CD4 T cell numbers and shifts their phenotype towards parenchymal protective cells. Moreover,

SUBMITTER: Gress AR 

PROVIDER: S-EPMC10728168 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature