Abstract
Recent work has suggested that current mouse models may underrepresent the complexity of human immune responses. While most mouse immunology studies utilize inbred mouse strains, it is unclear if conclusions drawn from inbred mice can be extended to all mouse strains or generalized to humans. We recently described a “surrogate activation marker” approach that could be used to track polyclonal CD8 T cell responses in inbred and outbred mice and noted substantial discord in the magnitude and kinetics of CD8 T cell responses in individual outbred mice following infection. However, how the memory CD8 T cell response develops following infection and the correlates of memory CD8 T cell-mediated protection against re-infection in outbred mice remains unknown. In this study, we investigated development of pathogen-specific memory CD8 T cell responses in inbred C57B/6 and outbred National Institutes of Health Swiss mice following lymphocytic choriomeningitis virus or L. monocytogenes infection. Interestingly, the size of the memory CD8 T cell pool generated and rate of phenotypic progression was considerably more variable in individual outbred compared to inbred mice. Importantly, while prior infection provided both inbred and outbred cohorts of mice with protection against re-infection that was dependent on the dose of primary infection, levels of memory CD8 T cells generated and degree of protection against re-infection did not correlate with primary infection dose in all outbred mice. While variation in CD8 T cell responses to infection is not entirely surprising due to the genetic diversity present, analysis of infection-induced immunity in outbred hosts may reveal hidden complexity in CD8 T cell responses in genetically diverse populations and might help us further bridge the gap between mouse and human studies.
Highlights
Much of our current understanding of immunology has been learned through the study of laboratory mice, and most of these studies have utilized one or two inbred mouse strains
Recent work from our laboratory demonstrated that expression of CD8α and CD11a could be used to identify Ag-specific CD8 T cell responses in both inbred and outbred mouse strains [10]
To further examine kinetics of polyclonal CD8 T cell responses, inbred C57B/6 (B6) and outbred National Institutes of Health (NIH) Swiss (Swiss) mice were infected with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) (Figure 1A)
Summary
Much of our current understanding of immunology has been learned through the study of laboratory mice, and most of these studies have utilized one or two inbred mouse strains. Genetic homozygosity allows for empirical analysis of how individual genes impact the immune response. These tools developed for use in inbred mice allow for detailed analyses of the immune response in the setting of autoimmunity, following infection and/or vaccination, and in response to tumors, and have provided valuable information for the development of therapeutic interventions during disease states. This work has suggested that the environment in which laboratory mice are housed and their exposure to infections that humans are naturally exposed to can impact the composition of the immune system, and that mouse models that include microbial exposure could be used as a tool to study immunological responses in free-living organisms such as humans [7, 8]. While inclusion of multiple pathogen exposures will certainly inform our understanding of the immune system, it is still unclear whether the knowledge that we have gained utilizing a limited number of inbred mouse strains holds true for all mouse strains or can be generalized to humans
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
