Circulating KLRG1+ memory T cells retain the flexibility to become tissue-resident

KLRG1+ CD8 T cells persist for months after acute infections are cleared
and maintain high levels of effector molecules, contributing essential
protective immunity against systemic pathogens. Upon secondary infection,
these long-lived effector cells (LLECs) are incapable of forming other
circulating KLRG1− memory subsets such as central and effector
memory T cells. Thus, KLRG1+ memory T cells are frequently referred to as
a terminally differentiated population that is relatively short lived.
Here, we show that during infection, effector cells derived from LLEC
rapidly enter nonlymphoid tissues and reduce pathogen burden, but are
largely dependent on receiving antigen cues from vascular endothelial
cells. Single-cell RNA sequencing revealed that secondary memory cells in
nonlymphoid tissues arising from either KLRG1+ or KLRG1− memory
precursors developed a similar transcriptional signature. Thus, although
KLRG1+ memory T cells cannot differentiate into other circulating memory
populations, they still retain the flexibility to enter tissues and
establish residency.