Promyelocytic zinc finger transcription factor (PLZF) is an important transcription factor expressed by natural killer T (NKT) cells and a variety of other innate T cells. Development of these PLZF positive cells require the adaptor molecule SLAM- associated protein (SAP) and the interaction of the signaling lymphocyte activation molecule (SLAM) family member receptors in addition to TCR stimulation. However, it remains unclear how these interactions influence the development of innate thymocytes. We have found that costimulation of pre-selection double positive (PS-DP) thymocytes with an agonist to the SLAM family receptor Ly108 greatly enhances PLZF expression compared to TCR stimulation alone. Furthermore, PLZF expressing cells were reduced in Ly108 deficient mice and increased in transgenic mice expressing a hyperactive Ly108 isoform. Costimulaiton with Ly108 also increased the expression of Egr-2 and the binding of Egr-2 to the PLZF (Zbtb16) promoter. Surprisingly costimulation with CD28 was unable to enhance Egr-2 nor PLZF expression in vitro suggesting that Ly108 has a unique role in PLZF expression. This work provides a novel mechanism by which innate thymocyte development is regulated via Ly108 and possibly other SLAM family receptor interactions.
- Copyright © 2013 by The American Association of Immunologists, Inc.