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

被引:69
作者
Fraser, Kathryn A. [1 ,2 ]
Schenkel, Jason M. [1 ,2 ]
Jameson, Stephen C. [2 ]
Vezys, Vaiva [1 ,2 ]
Masopust, David [1 ,2 ]
机构
[1] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA
基金
美国国家卫生研究院;
关键词
SPARE RESPIRATORY CAPACITY; IN-VIVO; TERMINAL DIFFERENTIATION; TELOMERASE ACTIVITY; OXIDATIVE STRESS; VIRAL-INFECTION; CUTTING EDGE; EFFECTOR; EXPRESSION; NAIVE;
D O I
10.1016/j.immuni.2013.07.003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:171 / 183
页数:13
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