BibTex format
@article{Kurokawa:2026:10.1371/journal.ppat.1013866,
author = {Kurokawa, R and Mtali, CS and Daniel, IJ and Einarsdottir, T and Reda, O and Irie, N and Sakhor, W and Niimura, K and Takatori, M and Sugata, K and Tye, CA and Satou, Y and Ono, M and Nomura, T},
doi = {10.1371/journal.ppat.1013866},
journal = {PLoS Pathog},
title = {Dynamics of lung-infiltrating virus-specific T cells associated with age-dependent SARS-CoV-2 pneumonia severity.},
url = {http://dx.doi.org/10.1371/journal.ppat.1013866},
volume = {22},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Coronavirus disease 2019 (COVID-19) pneumonia is prevalent in the elderly infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the mechanisms underlying its age-dependent pathogenesis remain unclear. In this study, we established a mouse-adapted SARS-CoV-2 strain infected Nr4a3-Tocky mouse model to examine T-cell dynamics associated with disease severity. Nr4a3-Tocky mice allow the analysis of the dynamics and induction of antigen-reactive T cells following antigen recognition in vivo using fluorescent Timer protein. SARS-CoV-2-infected adult mice exhibited transient body weight loss and recovery, whereas aged mice developed severe pneumonia. BALF viral RNA was comparable between 1-4 days post-inoculation (d.p.i.), but declined in adults at 5 d.p.i. Aged mice displayed stronger inflammation as indicated by scRNA-seq, and higher levels of inflammatory cytokines (TNF-α, CCL2, CXCL10 and IL-6) in BALF correlated with weight loss. Timer analysis revealed induction of antigen-reactive T cells in the adult lungs at 5 and 8 d.p.i., which inversely correlated with disease severity. Additionally, S-specific IFN-γ CD8 T cells were detected at 5 d.p.i. in adults, whereas detection of antigen-specific T cells was delayed in aged mice. These results suggest that the coexistence of age-related lung inflammation and delayed induction of antigen-specific T cells is linked to more severe pneumonia, while earlier T-cell responses are associated with improved viral control and milder disease. In this study, we utilized a novel mouse model enabling characterization of antigen-reactive T cells in the local tissue, and investigated inflammatory responses in the lung together with lung-infiltrating virus-specific T cells, finding the dynamics of these immunological parameters associated with the age of the mice. Our analysis provides new insights into understanding how age-related T-cell dysfunction is associated
AU - Kurokawa,R
AU - Mtali,CS
AU - Daniel,IJ
AU - Einarsdottir,T
AU - Reda,O
AU - Irie,N
AU - Sakhor,W
AU - Niimura,K
AU - Takatori,M
AU - Sugata,K
AU - Tye,CA
AU - Satou,Y
AU - Ono,M
AU - Nomura,T
DO - 10.1371/journal.ppat.1013866
PY - 2026///
TI - Dynamics of lung-infiltrating virus-specific T cells associated with age-dependent SARS-CoV-2 pneumonia severity.
T2 - PLoS Pathog
UR - http://dx.doi.org/10.1371/journal.ppat.1013866
UR - https://www.ncbi.nlm.nih.gov/pubmed/41533733
VL - 22
ER -