Transcriptional Repressor Blimp-1 Promotes CD8+ T Cell Terminal Differentiation and Represses the Acquisition of Central Memory T Cell Properties

被引:476
作者
Rutishauser, Rachel L. [1 ]
Martins, Gislaine A. [3 ]
Kalachikov, Sergey [2 ]
Chandele, Anmol [1 ]
Parish, Ian A. [1 ]
Meffre, Eric [1 ]
Jacob, Joshy [4 ]
Calame, Kathryn [3 ]
Kaech, Susan M. [1 ]
机构
[1] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA
[2] Columbia Univ, Coll Phys & Surg, Columbia Genome Ctr, New York, NY 10032 USA
[3] Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA
[4] Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr,Yerkes Natl Primate Ctr, Atlanta, GA 30322 USA
关键词
CHRONIC VIRAL-INFECTION; IL-7; RECEPTOR-ALPHA; IN-VIVO; B-CELLS; SELECTIVE EXPRESSION; LINEAGE RELATIONSHIP; GENE-EXPRESSION; EFFECTOR; HOMEOSTASIS; GENERATION;
D O I
10.1016/j.immuni.2009.05.014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
During acute infections, a small population of effector CD8(+) T cells evades terminal differentiation and survives as long-lived memory T cells. We demonstrate that the transcriptional repressor Blimp-1 enhanced the formation of terminally differentiated CD8(+) T cells during lymphocytic choriomeningitis virus (LCMV) infection, and Blimp-1 deficiency promoted the acquisition of memory cell properties by effector cells. Blimp-1 expression was preferentially increased in terminally differentiated effector and "effector memory" (Tem) CD8(+) T cells, and gradually decayed after infection as central memory (Tcm) cells developed. Blimp-1-deficient effector CD8(+) T cells showed some reduction in effector molecule expression, but primarily developed into memory precursor cells that survived better and more rapidly acquired several Tcm cell attributes, including CD62L and IL-2 expression and enhanced proliferative responses. These results reveal a critical role for Blimp-1 in controlling terminal differentiation and suppressing memory cell developmental potential in effector CD8(+) T cells during viral infection.
引用
收藏
页码:296 / 308
页数:13
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