title: Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting.
abstract: Memory CD8+ T cell quantity and quality determine protective efficacy against reinfection. Heterologous prime boost vaccination minimizes contraction of anamnestic effectors and maximizes memory CD8+ T cell quantity but reportedly erodes proliferative potential and protective efficacy. This study exploited heterologous prime boost vaccination to discover parameters regulating effector CD8+ T cell contraction and memory differentiation. When abundant memory T cells were established, boosting induced only 5-8 cell divisions, unusually rapid memory T cell differentiation as measured by phenotype and mitochondrial bioenergetic function, long-lived survival of 50% of effector T cells, and preservation of proliferative potential. Conversely, boosting in situations of low memory CD8+ T cell frequencies induced many cell divisions, increased contraction of effector cells, and caused senescence, low mitochondrial membrane potential, and poorly protective memory. Thus, anamnestic memory T cell differentiation is flexible, and abundant quantity can be achieved while maximizing protective efficacy and preserving proliferative potential.
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Fraser
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schenkel
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
authors.forename: Vaiva
authors.initials: V
authors.lastname: Vezys
authors.forename: David
authors.initials: D
authors.lastname: Masopust
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D007117:Immunization, Secondary / Q000379:methods*; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000956:Antigens, Viral
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