Ectopic expression of PLZF results in an RORγt positive cytotoxic T cell subset — ASN Events
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Ectopic expression of PLZF results in an RORγt positive cytotoxic T cell subset (#151)

Patrick W Darcy 1 2 , Derek B Sant'Angelo 1 2 3 4 5
  1. Rutgers Robert Wood Johnson Medical School, Rutgers University , New Brunswick , New Jersey, USA
  2. The Child Health Insitiute of New Jersey, Rutgers University, New Brunswick, NEW JERSEY, United States
  3. Department of Pediatrics, Rutgers University, New Brunswick, New Jersey, USA
  4. Rutgers Graduate School of Biomedical Sciences, Rutgers University, New Brunswick, New Jersey, USA
  5. Department of Pharmacology , Rutgers University, New Brunswick, New Jersey, USA

Promyelotic Leukemia Zinc Finger (PLZF), a member of the BTB-ZF transcription factor family, is a critical regulator of Natural Killer T (NKT) cell and Mucosal Associated Invariant T (MAIT) cell biology.  In the absence of PLZF, the development of both T cell subsets is stunted.  In addition, PLZF expression is required for the unique cytokine production capabilities of NKT cells and MAIT cells.  We investigated PLZF's role in T cell development and function using a mouse model in which conventional T cells expressed PLZF under the Lck promoter.   Specifically, we focused on a population of cytotoxic T cells that expressed the transcription factor RORγt upon ectopic expression of PLZF.  We were intrigued by this population for three reasons. (1) RORγt marks cells primed to produce IL-17. (2) Subsets of NKT cells (NKT17s) and MAIT cells express RORγt and produce IL-17 following primary activation.  (3) Naive wild-type cytotoxic T cells do not express RORγt.  Initially we established that the Lck.PLZF transgenic, RORγt expressing cytotoxic T cells were not an NKT cell or MAIT cell population by demonstrating that the Lck.PLZF transgenic RORγt expressing cytotoxic T cells possessed an unbiased TCR repertoire.  Lck.PLZF transgenic, RORγt expressing cytotoxic T cells displayed an NKT17/MAIT cell phenotype primed to produce IL-17 in response to activation, evidenced by the presence of IL-17 transcript within the cells in the absence of activation and by the production of IL-17 protein following primary activation.  In addition, the Lck.PLZF transgenic, RORγt expressing cytotoxic T cells expressed an array of cell surface molecules characteristic of NKT17s and MAIT cells.   Finally, Lck.PLZF transgenic, RORγt expressing cytotoxic T cells accumulated in non-lymphoid tissues, a phenotype associated with NKT17s and MAIT cells.  These results support the argument that co-expression of PLZF and RORγt confers a distinct phenotype upon T cells.