KLF2's role in T cell trafficking and retention in lymphoid and non-lymphoid tissues

Abstract

The transcription factor Kruppel-like Factor 2 (KLF2) is essential for naïve T cell trafficking, yet its significance in memory T cells is unclear. This thesis investigates the significance of KLF2 expression in CD4+ and CD8+ memory T cells. Using eGFP-KLF2 reporter mice, we identified KLF2 heterogeneity in the memory phase of an immune response. In chapter one, we distinguished KLF2 expression in subsets of CD8+ memory T cells. Resident memory T cells (TRM) were shown to down-regulate KLF2 in the parenchyma of non-lymphoid tissue. Using parabiosis, we identified rare circulating CD8+ memory T cells in the parenchyma of non-lymphoid tissue that have intermediate KLF2 expression. In chapter two, we investigate the relevance of the KLF2 downregulation in CD8+ TRM by forcing a target of KLF2, sphingosine 1 phosphate receptor 1 (S1PR1), using retroviral transduction. We went on to show that KLF2 can be downregulated by inflammatory cytokines via the P13K/AKT pathway independent of antigen exposure. Lastly, chapter four focuses on KLF2 heterogeneity in CD4+ memory T cells showing that KLF2LO cells had diminished lymph node egress. In summary, this work defines KLF2 heterogeneity in memory T cells as being significant for discerning whether a cell is retained in a particular tissue or continues to traffic throughout an organism.