The Kruppel, the Like, the Factor, the 2, and the Ology.

Abstract

This thesis project began with testing the role of IL-7 and Erk5 in regulation of KLF2 expression and SP maturation. We provide evidence that SP maturation occurs independently of both IL-7 and Erk5. Next we examined the direct effects of KLF2 deficiency in T cells. Here we made the surprising discovery that KLF2 deficiency causes cell extrinsic effects on wild type (WT) thymocytes using mixed bone marrow chimeras. In the third chapter we show that the cell extrinsic effects result in expression of the chemokine receptor CXCR3 and are dependent on IL-4 receptor signaling acting through the transcription factor eomesodermin. The cell extrinsic effects also lead to delayed thymocyte emigration and we investigate the mechanism for this emigration defect in chapter 4. This leads to the novel finding that CXCR3 is necessary for the maintenance of returning memory CD8 T cells in the thymus. In the fifth chapter, we identify a cell intrinsic expansion of PLZF+ T cells as the source of IL-4 in the KLF2 deficient thymus. We also show that the cell extrinsic effects lead to memory phenotype and function on bystander CD8 T cells. We show that this mechanism occurs in other gene deficiency models and in WT BALB/c mice.