Back to Search
Start Over
Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy.
- Source :
- Nature Communications; 12/18/2023, Vol. 14 Issue 1, p1-16, 16p
- Publication Year :
- 2023
-
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<superscript>HI</superscript> cells contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFP<superscript>LO</superscript> cells. By contrast, Nur77-GFP<superscript>LO</superscript> cells express markers of terminal exhaustion and cytotoxicity, and the trafficking receptor S1pr5, associated with vascular localization. A short course of immunotherapy targeting OX40<superscript>+</superscript> cells transiently expands CD4 T cell numbers and shifts their phenotype towards parenchymal protective cells. Moreover, OX40 agonist immunotherapy decreases the lung bacterial burden and extends host survival, offering an additive benefit to antibiotics. CD4 T cells from the cerebrospinal fluid of humans with HIV-associated tuberculous meningitis commonly express surface OX40 protein, while CD8 T cells do not. Our data thus propose OX40 as a marker of recently activated CD4 T cells at the infection site and a potential target for immunotherapy in tuberculosis. Marking of recently activated T cells may help further our understanding of immunity against Mycobacterium tuberculosis (Mtb). Here the authors use Nur77-GFP reporter mice infected with Mtb and systems data approaches to implicate OX40 as a marker for recently activated, functionally and transcriptome-wise distinct CD4 T cells, and as a potential target for immunotherapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
CD4 antigen
TUBERCULOSIS
ANTIGEN receptors
TUBERCULOUS meningitis
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 174298813
- Full Text :
- https://doi.org/10.1038/s41467-023-44152-8