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
Date
08/29/2007Pubmed ID
17723218Pubmed Central ID
PMC2034442DOI
10.1016/j.immuni.2007.07.010Scopus ID
2-s2.0-34548027000 (requires institutional sign-in at Scopus site) 1511 CitationsAbstract
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.
Author List
Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, Gapin L, Kaech SMMESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers
CD8-Positive T-Lymphocytes
Cytokines
Immunologic Memory
Inflammation
Interferon-gamma
Interleukin-12
Interleukin-15
Lectins, C-Type
Mice
Mice, Mutant Strains
Receptors, Immunologic
Receptors, Interleukin-7
T-Box Domain Proteins
