Memory CD8+ T cells provide essential specific immunity against previously encountered antigens, and formation of such cells is a fundamental goal of vaccination. Effective CD8+ T cell memory is thought to require cells that persist at elevated frequencies long after antigen clearance, engage in rapid and robust expansion after reencounter with antigen and quickly re-acquire effector functions after re-stimulation. The overall focus of this proposal is to extend preliminary studies that define a special population of memory CD8 T cells that carry out highly efficient protective immunity against various pathogens - to determine how they achieve this protective effect, how this population of cells is maintained, and how these cells relate to populations arising in mice that arise naturally (following exposure to natural mouse pathogens) in order to understand how these cells relate to natural immunity.
Cells of the immune system are critical for control of pathogens (i.e. damaging infectious agents) and are the goal of vaccination. Populations of immune cells called memory CD8 T cells can eliminate many viral and bacterial pathogens: We have characterize a population of memory cells called 'long-lived effector cells' that we showed are highly efficient at pathogen control. We wish to understand how such cells are generated, how they mediate such impressive protection against infection, and to extend our findings away from typical experiments using genetically pure, immunologically nave mice to the more realistic situation of genetically mixed mice exposed to normal mouse microbes and pathogens - as situation more relevant to humans.
| Masopust, David; Sivula, Christine P; Jameson, Stephen C (2017) Of Mice, Dirty Mice, and Men: Using Mice To Understand Human Immunology. J Immunol 199:383-388 |
| Beura, Lalit K; Hamilton, Sara E; Bi, Kevin et al. (2016) Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532:512-6 |
