KLF2 overrides the resident memory CD8 T cell differentiation program, in opposition to KLF3

However, it is unclear whether independent, coordinated expression of these regulators is required to determine residency versus recirculation, or whether there is a hierarchy, with some factors playing a dominant role in controlling T cell trafficking. We report that ablation of the gene encoding Kruppel-like factor 2 (KLF2) during CD8+ T cell activation leads to rapid transcriptional reprograming, such that effector T cells fail to recirculate and prematurely acquire canonical phenotypic and transcriptional characteristics of resident memory cells (TRM).

Klf2-deficient memory CD8+ T cells retained the capacity to undergo recall responses, including in vivo pathogen control. These data suggest KLF2 diverts CD8+ T cells from the TRM differentiation program. In contrast, ablation of another member of the KLF family, KLF3, enhanced differentiation of some recirculating T cell subsets and limited production of TRM in lymphoid tissues.