Research Scientist University of Louisville Louisville, Kentucky, United States
Disclosure(s):
Divyasha Saxena, PhD: No financial relationships to disclose
Introduction/Rationale: Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Impaired and dysregulated host immunities, such as impaired coordination and disruption of CD4/CD8 T-cell-mediated virus-specific adaptive immune responses to SARS-CoV-2, have been hypothesized as age-related risk factors in COVID-19 disease severity. However, the characteristics and heterogeneity of CD4/CD8 T cell subsets that respond to SARS-CoV-2 remain elusive. In the present study, we focused on investigating those subsets and there role in COVID-19 infection.
Methods: We established an age-dependent COVID-19 model by infecting middle-age mice (7-8 months old) or young mice (6-8 weeks old) with 100 or 500pfu of a mouse adapted SARS-CoV-2 virus (SARS2-N501YMA30). Lung, spleen tissues and blood harvested at 60 and 90 days post infection (dpi) were subjected to flow-cytometry and CyTOF for CD4/CD8 T cell profiling. Data was analyzed using FlowJo_v10.10.0 software.
Results: Only middle-age mice showed an average weight loss of 10% and 20% in low (100pfu) and high (500pfu) viral dose infected group respectively. Immune profiling revealed increase in the CD11b, CD11c expressing CD4/CD8 T cell subsets in the infected mice. These infection-prompted subsets increased significantly in middle-age mice and were found to contribute in effector functions as well as consist T cell-mediated immune memory, characterized by higher Granzyme B and Perforin expression.
Conclusion: This study characterizes CD11b, CD11c expressing CD4/CD8 T cell subsets with potent antiviral effects, which is in accord with the reported data of association of CD11b and CD11c T cell with increased cytotoxic activity in other viral infections like Influenza, RSV. Further analysis of these immune cells is underway to better understand their roles in driving protective or pathogenic immune responses upon SARS-CoV-2 infection in mice.
