Preexisting High Frequencies of Memory CD8+ T Cells Favor Rapid Memory Differentiation and Preservation of Proliferative Potential upon Boosting

• Published in: Immunity (Cambridge, Mass.) Vol. 39; no. 1; pp. 171 - 183
• Main Authors: Fraser, Kathryn A., Schenkel, Jason M., Jameson, Stephen C., Vezys, Vaiva, Masopust, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.07.2013; Elsevier Limited
• Subjects: Animals; Antigens, Viral - immunology; Cancer; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - immunology; Cell division; Cell Proliferation; Cell Survival - immunology; Cloning; Flow Cytometry; Gene expression; Immunization, Secondary - methods; Immunologic Memory - immunology; Immunophenotyping; Infections; Lymphocytes; Metabolism; Mice; Mice, Inbred C57BL; Mitochondria - immunology; Mitochondria - metabolism; Preservation; Studies; Time Factors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.07.003

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. •Amnestic CD8 T cell fate and function depends on precursor frequency before boosting•Memory differentiation is accelerated during recall responses•Abundant CD8 T cell memory quantity without senescence can be achieved by vaccination•Reductionist studies that dilute memory CD8 T cell frequencies enhance senescence