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PMID: 19664941 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties.

Immunity ·Vol. 31 ·No. 2 ·2009-08-21 ·Pages 296-308

Rutishauser RL, Martins GA, Kalachikov S, Chandele A, Parish IA, Meffre E, Jacob J, Calame K, Kaech SM

Abstract

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.

MeSH Terms
Animals CD8-Positive T-Lymphocytes/immunology,virology Cell Differentiation/immunology Cytokines/immunology,metabolism Gene Expression Profiling Immunologic Memory Lymphocytic Choriomeningitis/immunology Lymphocytic choriomeningitis virus/immunology Mice Mice, Inbred C57BL Mice, Knockout Positive Regulatory Domain I-Binding Factor 1 Transcription Factors/genetics,metabolism Transcriptional Activation/immunology
Chemicals
Cytokines Prdm1 protein, mouse Transcription Factors Positive Regulatory Domain I-Binding Factor 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rutishauser Rachel L
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Martins Gislâine A
Kalachikov Sergey
Chandele Anmol
Parish Ian A
Meffre Eric
Jacob Joshy
Calame Kathryn
Kaech Susan M
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2009.05.014
Published
2009-08-21
Epub
2009-00-06
Pages
296-308
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2783637
Subset
IM
Grants
NIAID NIH HHS · R01 AI043576 · United States
NIAID NIH HHS · R21 AI077075-01 · United States
NIAID NIH HHS · R01-AI43576 · United States
NIAID NIH HHS · R21-AI077075 · United States
NIGMS NIH HHS · TG 5T32GM07205 · United States
NIAID NIH HHS · R01-AI066232 · United States
NIAID NIH HHS · R01-AI50659 · United States
NIGMS NIH HHS · T32 GM007205 · United States
NIAID NIH HHS · R21 AI077075 · United States
NIAID NIH HHS · R01 AI066232 · United States
NIAID NIH HHS · R01 AI050659 · United States
Databases
GEO
GSE17211
Corrections
CommentIn
PMID: 19699168
External Links
PubMed source DOI: 10.1016/j.immuni.2009.05.014 PMC Full Text View journal details
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