PLZF Induces the Spontaneous Acquisition of Memory/Effector Functions in T Cells Independently of NKT Cell-Related Signals

Abstract

The broad complex, tramtrack, bric-a-brac–zinc finger (BTB-ZF) transcription factor promyelocytic leukemia zinc finger (PLZF) is required for development of the characteristic innate/effector functions of NKT cells. In this study, we report the characterization and functional analysis of transgenic mouse T cells with forced expression of PLZF. PLZF expression was sufficient to provide some memory/effector functions to T cells without the need for Ag stimulation or proliferation. The acquisition of this phenotype did not require the proliferation typically associated with T cell activation. Furthermore, PLZF transgenic cells maintained a diverse TCR repertoire, indicating that there was no preferential expansion of specific clones. Functionally, PLZF transgenic CD4 and CD8 lymphocytes were similar to wild type memory cells, in that they had similar requirements for costimulation and exhibited a similar pattern of cytokine secretion, with the notable exception that transgenic T cells produced significantly increased levels of IL-17. Whereas transgene-mediated PLZF expression was not sufficient to rescue NKT cell development in Fyn- or signaling lymphocytic activation-associated protein (SAP)-deficient mice, the acquisition of memory/effector functions induced by PLZF in conventional T cells was independent of Fyn and SAP. These data show that PLZF is sufficient to promote T cell effector functions and that PLZF acts independently of SAP- and Fyn-mediated signaling pathways.

Metabolic regulator Fnip1 is crucial for iNKT lymphocyte development

“…S6). Previous studies have suggested that PLZF expression is tightly regulated during iNKT cell development, and is down-regulated following maturation of iNKT cells to stage 3 (17,29,30). In line with this, we found that PLZF expression in WT mice was downregulated during the transition from stage 2 to stage 3 ( Fig.…”

“…PLZF expression was persistently elevated in of late iNKT cell markers, such as CD122, NK1.1, and NKG2D (17,29,30). These studies suggest that iNKT cell development is exquisitely sensitive to levels of PLZF.…”

TLR-Induced Cytokines Promote Effective Proinflammatory Natural Th17 Cell Responses

“…PLZF defines not merely the phenotype of iNKT cells, it directs their effector program and is implicated in their proapoptotic propensity (16,39,40). Transgenic expression of PLZF during T cell development induced a T cell-intrinsic program leading to an increase in peripheral CD44 high memory/effector T cells (41,42). These transgenic T cells could produce large amounts of several cytokines upon primary activation without further peripheral polarization, which suggests that PLZF directly turns on the effector program in thymocytes that otherwise would have been selected as naive T cells.…”

Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function

“…In addition to iNKT cells, PLZF controls other lymphoid effector programs and is involved in many major developmental and biological processes, such as megakaryocytic development, stem cell renewal, limb development, and tumorigenesis (8,(32)(33)(34)(35). PLZF nuclear localization to the NBs has been proposed to be important for its function.…”