Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor

Immunity. 2007 Aug;27(2):281-95. doi: 10.1016/j.immuni.2007.07.010.

Abstract

As acute infections resolve, effector CD8(+) T cells differentiate into interleukin-7 receptor(lo) (IL-7R(lo)) short-lived effector cells (SLECs) and IL-7R(hi) memory precursor effector cells (MPECs) capable of generating long-lived memory CD8(+) T cells. By using another SLEC marker, KLRG1, we found that KLRG1(hi) effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7R(hi) MPECs, KLRG1(hi) IL-7R(lo) SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytokines / metabolism*
  • Immunologic Memory*
  • Infections / immunology
  • Infections / microbiology
  • Infections / virology
  • Inflammation / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-15 / metabolism
  • Mice
  • Mice, Mutant Strains
  • Receptors, Immunologic / analysis
  • Receptors, Immunologic / metabolism
  • Receptors, Interleukin-7 / metabolism
  • T-Box Domain Proteins / metabolism*

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-15
  • Klrg1 protein, mouse
  • Receptors, Immunologic
  • Receptors, Interleukin-7
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-12
  • Interferon-gamma