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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.
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机构:
Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

Martins, Gislaine A.
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Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

Kalachikov, Sergey
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Columbia Univ, Coll Phys & Surg, Columbia Genome Ctr, New York, NY 10032 USA Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

Chandele, Anmol
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机构:
Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

Parish, Ian A.
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Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

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Calame, Kathryn
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机构:
Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA

Kaech, Susan M.
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h-index: 0
机构:
Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA
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
来源:
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.
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页码:296 / 308
页数:13
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