KLF2 and S1Pr1: Aiding in memory T cell trafficking and retention in non-lymphoid tissue (173.16)

Abstract Memory T cells, unlike naïve T cells, have the capacity to traffic and be retained in non-lymphoid tissue (NLT). Because most infections originate in NLT and early detection of pathogens can lead to a more effective immune response, identifying factors contributing to memory T cell residence in NLT is an important aspect of memory T cell potential. The transcription factor kruppel-like factor 2 (KLF2) controls naive T cell trafficking (primarily through inducing sphingosine 1 phosphate receptor 1 (S1Pr1)), yet KLF2 expression in memory T cells has not been extensively addressed. Using eGFP-KLF2 reporter mice we report that almost all CD8+ memory T cells in lymphoid tissue express KLF2, yet the vast majority of CD8+ memory T cells in NLT (including small intestine, salivary glands, kidney and brain) are KLF2lo. Forced-expression of the KLF2 target gene S1Pr1, using retroviral transduction, caused a decrease in memory CD8+ T cells in NLT versus spleen, confirming a functional consequence of S1Pr1 down-regulation. We also showed that inflammatory cytokine milieu causes a decrease in KLF2 protein in the absence of antigen. Our data suggest that local cues from the non-lymphoid environment, including cytokines, cause a decrease in KLF2 and S1Pr1 leading to a cessation in CD8+ memory T cell trafficking that aids in memory T cell retention in NLT.