Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection.
PLoS Pathog
; 14(1): e1006810, 2018 01.
Article
in En
| MEDLINE
| ID: mdl-29293660
ABSTRACT
Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.
Full text:
1
Database:
MEDLINE
Main subject:
Respiratory Syncytial Virus Infections
/
CD8-Positive T-Lymphocytes
/
Immune System Diseases
/
Immunologic Memory
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
PLoS Pathog
Year:
2018
Type:
Article
Affiliation country:
United States