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

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.

• Authors: Nikhil S Joshi, Weiguo Cui, Anmol Chandele, Heung Kyu Lee, David R Urso, James Hagman, Laurent Gapin, Susan M Kaech
• Journal: Immunity (Immunity) Vol. 27 Issue 2 Pg. 281-95 (Aug 2007) ISSN: 1074-7613 [Print] United States
• PMID: 17723218 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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