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

Immunity. 2009 Aug 21;31(2):296-308. doi: 10.1016/j.immuni.2009.05.014. Epub 2009 Aug 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation / immunology
  • Cytokines / immunology
  • Cytokines / 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
  • Transcription Factors / metabolism*
  • Transcriptional Activation / immunology*

Substances

  • Cytokines
  • Prdm1 protein, mouse
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1

Associated data

  • GEO/GSE17211