title: Memory CD8 T-cell compartment grows in size with immunological experience.
abstract: Memory CD8 T cells, generated by natural pathogen exposure or intentional vaccination, protect the host against specific viral infections. It has long been proposed that the number of memory CD8 T cells in the host is inflexible, and that individual cells are constantly competing for limited space. Consequently, vaccines that introduce over-abundant quantities of memory CD8 T cells specific for an agent of interest could have catastrophic consequences for the host by displacing memory CD8 T cells specific for all previous infections. To test this paradigm, we developed a vaccination regimen in mice that introduced as many new long-lived memory CD8 T cells specific for a single vaccine antigen as there were memory CD8 T cells in the host before vaccination. Here we show that, in contrast to expectations, the size of the memory CD8 T-cell compartment doubled to accommodate these new cells, a change due solely to the addition of effector memory CD8 T cells. This increase did not affect the number of CD4 T cells, B cells or naive CD8 T cells, and pre-existing memory CD8 T cells specific for a previously encountered infection were largely preserved. Thus, the number of effector memory CD8 T cells in the mammalian host adapts according to immunological experience. Developing vaccines that abundantly introduce new memory CD8 T cells should not necessarily ablate pre-existing immunity to other infections.
authors.affiliation: Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Vaiva
authors.initials: V
authors.lastname: Vezys
authors.forename: Andrew
authors.initials: A
authors.lastname: Yates
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Casey
authors.forename: Gibson
authors.initials: G
authors.lastname: Lanier
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Rustom
authors.initials: R
authors.lastname: Antia
authors.forename: David
authors.initials: D
authors.lastname: Masopust
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002478:Cells, Cultured; D018960:Hyaluronan Receptors / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D019041:L-Selectin / Q000378:metabolism; D018655:Lymphocyte Count; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D016056:Immunodominant Epitopes; D014765:Viral Vaccines; D019041:L-Selectin