Journal
PLOS PATHOGENS
Volume 14, Issue 10, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1007365
Keywords
-
Categories
Funding
- National Institute of Neurological Diseases and Stroke of the National Institutes of Health [R01 NS088367, R01 NS092662]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR002014, TL1TR002016] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS092662, R01NS088367, F32NS106730] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Tissue-resident memory CD8 T (T-RM) cells defend against microbial reinfections at mucosal barriers; determinants driving durable T-RM cell responses in non-mucosal tissues, which often harbor opportunistic persistent pathogens, are unknown. JC polyomavirus (JCPyV) is a ubiquitous constituent of the human virome. With altered immunological status, JCPyV can cause the oft-fatal brain demyelinating disease progressive multifocal leukoencephalo-pathy (PML). JCPyV is a human-only pathogen. Using the mouse polyomavirus (MuPyV) encephalitis model, we demonstrate that CD4 T cells regulate development of functional antiviral brain-resident CD8 T cells (bT(RM)) and renders their maintenance refractory to systemic CD8 T cell depletion. Acquired CD4 T cell deficiency, modeled by delaying systemic CD4 T cell depletion until MuPyV-specific CD8 T cells have infiltrated the brain, impacted the stability of CD8 bT(RM), impaired their effector response to reinfection, and rendered their maintenance dependent on circulating CD8 T cells. This dependence of CD8 bT(RM) differentiation on CD4 T cells was found to extend to encephalitis caused by vesicular stomatitis virus. Together, these findings reveal an intimate association between CD4 T cells and homeostasis of functional bT(RM) to CNS viral infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available