Immunologic function of Virtual Memory CD8+ T cells & Role of KLF2 in effector CD4+ T cell lineage commitment

Abstract

During my Ph.D. training, my research has been focused on two distinct topics: investigating the immunologic fuction of Virtual Memory CD8+ T cells; and elucidating the role of KLF2 in effector CD4+ T cell lineage commitment. In the first part (Chaper 2), we investigate the immunologic properties of foreign-antigen specific memory-phenotype T cells, termed Virtual Memory (VM). Our data indicates that VM cells differ functionally from "true memory" cells, yet VM cells efficiently control a bacterial (Listeria monocytogenes) infection. These data support the novel concept that naturally occurring VM cells contribute to "pre-immune" resistance to infection. In the second part (Chapter 3), we find that expression of the transcription factor Kruppel-like factor 2 (KLF2) expression varies in distinct Th subsets, and downregulation of KLF2 and the trafficking molecule S1PR1 (the well-defined target of KLF2) is required for Tfh differentiation. In addition to promoting S1PR1 expression, we also find that KLF2 induces expression of Blimp-1, which is known to oppose Tfh differentiation. Furthermore, KLF2 also promotes expression of T-bet and Gata3, and enhances Th1 differentiation. These data reveal that KLF2 plays an important role in dictating the lineage differentiation of CD4+ T cells.